Significant Genotypic Differences Research Articles

EZH2 G553C significantly increases the risk of brain metastasis from lung cancer due to salt bridge instability

BackgroundThe incidence and mortality of lung cancer is the highest in China and the world. Brain is the most common distant metastasis site of lung cancer. Its transfer mechanism and predictive biomarkers are still unclear. EZH2 participates in the catalysis of transcriptional inhibition complex, mediates chromatin compactness, leads to the silencing of its downstream target genes, participates in the silencing of multiple tumor suppressor genes, and is related to cell proliferation, apoptosis and cycle regulation. In physiology, EZH2 has high activity in stem cells or progenitor cells, inhibits genes related to cell cycle arrest and promotes self-renewal. To detect the expression and mutation of EZH2 gene in patients with brain metastasis of lung cancer, and provide further theoretical basis for exploring the pathogenesis of brain metastasis of lung cancer and finding reliable biomarkers to predict brain metastasis of lung cancer.MethodsThis study investigated susceptible genes for brain metastasis of lung cancer. The second-generation sequencing technology was applied to screen the differential genes of paired samples (brain metastasis tissues, lung cancer tissues and adjacent tissues) of lung cancer patients with brain metastasi.ResultsIt revealed that there was a significant difference in the G553C genotype of EZH2 between lung cancer brain metastasis tissues and lung cancer tissues (p = 0.045). The risk of lung cancer brain metastasis in G allele carriers was 2.124 times higher than that in C allele carriers. Immunohistochemistry showed that compared with lung cancer patients and lung cancer patients with brain metastasis, the expression level of EZH2 in lung cancer tissues of lung cancer patients was significantly higher than that in adjacent lung tissues (p < 0.0001), and higher than that in brain metastasis tissues (p = 0.0309). RNA in situ immunohybridization showed that EZH2 mRNA expression was gradually high in lung cancer adjacent tissues, lung cancer tissues and lung cancer brain metastasis tissues.ConclusionsEZH2 G553C polymorphism contributes to the prediction of brain metastasis of lung cancer, in which G allele carriers are more prone to brain metastasis.

Therapeutic efficacy of generic artemether–lumefantrine in the treatment of uncomplicated malaria in Ghana: assessing anti-malarial efficacy amidst pharmacogenetic variations

BackgroundDespite efforts made to reduce morbidity and mortality associated with malaria, especially in sub-Saharan Africa, malaria continues to be a public health concern that requires innovative efforts to reach the WHO-set zero malaria agenda. Among the innovations is the use of artemisinin-based combination therapy (ACT) that is effective against Plasmodium falciparum. Generic artemether–lumefantrine (AL) is used to treat uncomplicated malaria after appropriate diagnosis. AL is metabolized by the cytochrome P450 family of enzymes, such as CYP2B6, CYP3A4 and CYP3A5, which can be under pharmacogenetic influence. Pharmacogenetics affecting AL metabolism, significantly influence the overall anti-malarial activity leading to variable therapeutic efficacy. This study focused on generic AL drugs used in malarial treatment as prescribed at health facilities and evaluated pharmacogenomic influences on their efficacy.MethodsPatients who have been diagnosed with malaria and confirmed through RDT and microscopy were recruited in this study. Blood samples were taken on days 1, 2, 3 and 7 for parasite count and blood levels of lumefantrine, artemisinin, desbutyl-lumefantrine (DBL), and dihydroartemisinin (DHA), the active metabolites of lumefantrine and artemether, respectively, were analysed using established methods. Pharmacogene variation analysis was undertaken using iPLEX microarray and PCR–RFLP.ResultsA total of 52 patients completed the study. Median parasite density from day 1 to 7 ranged from 0–2666/μL of blood, with days 3 and 7 recording 0 parasite density. Highest median plasma concentration for lumefantrine and desbutyl lumefantrine, which are the long-acting components of artemisinin-based combinations, was 4123.75 ng/mL and 35.87 ng/mL, respectively. Day 7 plasma lumefantrine concentration across all generic ACT brands was ≥ 200 ng/mL which potentially accounted for the parasitaemia profile observed. Monomorphism was observed for CYP3A4 variants, while there were observed variations in CYP2B6 and CYP3A5 alleles. Among the CYP3A5 genotypes, significant differences in genotypes and plasma concentration for DBL were seen on day 3 between 1/*1 versus *1/*6 (p = 0.002), *1/*3 versus *1/*6 (p = 0.006) and *1/*7 versus *1/*6 (p = 0.008). Day 7 plasma DBL concentrations showed a significant difference between *1/*6 and *1/*3 (p = 0.026) expressors.ConclusionsThe study findings show that CYP2B6 and CYP3A5 pharmacogenetic variations may lead to higher plasma exposure of AL metabolites.

Deletion of FNDC5/irisin modifies murine osteocyte function in a sex-specific manner

Irisin, released from exercised muscle, has been shown to have beneficial effects on numerous tissues but its effects on bone are unclear. We found significant sex and genotype differences in bone from wildtype (WT) mice compared to mice lacking Fndc5 (knockout [KO]), with and without calcium deficiency. Despite their bone being indistinguishable from WT females, KO female mice were partially protected from osteocytic osteolysis and osteoclastic bone resorption when allowed to lactate or when placed on a low-calcium diet. Male KO mice have more but weaker bone compared to WT males, and when challenged with a low-calcium diet lost more bone than WT males. To begin to understand responsible molecular mechanisms, osteocyte transcriptomics was performed. Osteocytes from WT females had greater expression of genes associated with osteocytic osteolysis and osteoclastic bone resorption compared to WT males which had greater expression of genes associated with steroid and fatty acid metabolism. Few differences were observed between female KO and WT osteocytes, but with a low-calcium diet, the KO females had lower expression of genes responsible for osteocytic osteolysis and osteoclastic resorption than the WT females. Male KO osteocytes had lower expression of genes associated with steroid and fatty acid metabolism, but higher expression of genes associated with bone resorption compared to male WT. In conclusion, irisin plays a critical role in the development of the male but not the female skeleton and protects male but not female bone from calcium deficiency. We propose irisin ensures the survival of offspring by targeting the osteocyte to provide calcium in lactating females, a novel function for this myokine.

Deletion of FNDC5/irisin modifies murine osteocyte function in a sex-specific manner.

Irisin, released from exercised muscle, has been shown to have beneficial effects on numerous tissues but its effects on bone are unclear. We found significant sex and genotype differences in bone from wildtype (WT) mice compared to mice lacking Fndc5 (knockout [KO]), with and without calcium deficiency. Despite their bone being indistinguishable from WT females, KO female mice were partially protected from osteocytic osteolysis and osteoclastic bone resorption when allowed to lactate or when placed on a low-calcium diet. Male KO mice have more but weaker bone compared to WT males, and when challenged with a low-calcium diet lost more bone than WT males. To begin to understand responsible molecular mechanisms, osteocyte transcriptomics was performed. Osteocytes from WT females had greater expression of genes associated with osteocytic osteolysis and osteoclastic bone resorption compared to WT males which had greater expression of genes associated with steroid and fatty acid metabolism. Few differences were observed between female KO and WT osteocytes, but with a low-calcium diet, the KO females had lower expression of genes responsible for osteocytic osteolysis and osteoclastic resorption than the WT females. Male KO osteocytes had lower expression of genes associated with steroid and fatty acid metabolism, but higher expression of genes associated with bone resorption compared to male WT. In conclusion, irisin plays a critical role in the development of the male but not the female skeleton and protects male but not female bone from calcium deficiency. We propose irisin ensures the survival of offspring by targeting the osteocyte to provide calcium in lactating females, a novel function for this myokine.

Nicotinic Receptor Alpha-5 Subunit Gene Polymorphism is Associated with Heavy Smoking Under a Range of Nicotine Dosing Conditions.

This study aimed to assess the role of the rs16969968 variant of nicotinic receptor alpha-5 subunit in regulating smoking behavior and nicotine intake in response to nicotine manipulations among dependent smokers in a naturalistic environment. Sixty-nine adults (19 females) smoking 10 or more cigarettes per day were asked to complete four 2-week study phases during which they smoked exclusively one of two types of Spectrum nicotine research cigarettes (FTC nicotine yield 0.8 and 1.6mg, respectively), their usual brand of cigarettes, or their usual brand of cigarettes while wearing a 21-mg nicotine patch. Measurements included rs16969968 genotype, number of cigarettes per day, smoking topography, and plasma cotinine. Compared to controls (G/G carriers), A allele carriers reported smoking 4 to 5 more cigarettes per day across all conditions (all ps < .05). Mean total smoke volume per day and cotinine were greater in A allele carriers than in controls (ps = 0.05, 0.046, respectively). No significant genotype differences were found in smoking compensation indices for the switch from Medium to High nicotine yield cigarettes. Nicotine patch-induced reductions in cigarettes smoked per day and total smoke volume per day showed significant interactions between genotype and pre-patch levels, heavier smokers showing greater effects of genotype (p = .052 and p =.006, respectively). Results suggest that the rs16969968 variants regulate heaviness of smoking primarily by their impact on daily numbers of cigarettes smoked, but no genotype differences were found in smoking compensation after switching from Medium to High nicotine cigarettes. The differences in daily cigarette consumption between rs16969968 risk-allele carriers and controls are shown to be consistent regardless of manipulations of cigarette nicotine content and transdermal nicotine supplementation and markedly greater among dependent smokers than those observed in the general smoker populations. G/G allele carriers, relative to A allele carriers, appeared to be more sensitive to the nicotine patch manipulation, reducing their smoking to a greater extent. These findings support continued efforts in the development of personalized intervention strategies to reduce the rs16969968-conveyed genetic propensity for heavy smoking.

CYP2C8 rs11572080 and CYP3A4 rs2740574 risk genotypes in paclitaxel-treated premenopausal breast cancer patients

Breast cancer (BC) is the most prevalent malignancy in women globally. At time of diagnosis, premenopausal BC is considered more aggressive and harder to treat than postmenopausal cases. Cytochrome P450 (CYP) enzymes are responsible for phase I of estrogen metabolism and thus, they are prominently involved in the pathogenesis of BC. Moreover, CYP subfamily 2C and 3A play a pivotal role in the metabolism of taxane anticancer agents. To understand genetic risk factors that may have a role in pre-menopausal BC we studied the genotypic variants of CYP2C8, rs11572080 and CYP3A4, rs2740574 in female BC patients on taxane-based therapy and their association with menopausal status. Our study comprised 105 female patients with histologically proven BC on paclitaxel-therapy. They were stratified into pre-menopausal (n = 52, 49.5%) and post-menopausal (n = 53, 50.5%) groups. Genotyping was done using TaqMan assays and employed on Quantstudio 12 K flex real-time platform. Significant increased frequencies of rs11572080 heterozygous CT genotype and variant T allele were established in pre-menopausal group compared to post-menopausal group (p = 0.023, 0.01, respectively). Moreover, logistic regression analysis revealed a significant association between rs11572080 CT genotype and premenopausal BC. However, regarding rs2740574, no significant differences in genotypes and allele frequencies between both groups were detected. We reported a significant association between CYP2C8 genotypic variants and premenopausal BC risk in Egyptian females. Further studies on larger sample sizes are still needed to evaluate its importance in early prediction of BC in young women and its effect on treatment outcome.

Correlation and Path Analysis Studies in Mungbean [Vigna radiata (L.) Wilczek] under Arid Environment of Western Rajasthan

Background: Mungbean is an important grain legume crop. It contains a high amount of protein, carbohydrates, vitamins and minerals. The productivity of this crop is still low, hence efforts should be made to improve the yield of mungbean by keeping knowledge about association between seed yield and its components. Thus, the present investigation was aimed to determine the correlation and path coefficient analysis for seed yield and its attributing traits in mungbean. Methods: Seventy-nine diverse genotypes of mungbean were evaluated during Kharif 2017-18 for eleven quantitative traits in randomized block design with three replications at the Experimental farm, Department of Genetics and Plant Breeding, College of Agriculture, Swami Keshwanand Rajasthan Agricultural University, Bikaner, Rajasthan. Result: Significant genotypic differences were observed for all the traits studied indicating a considerable amount of variation among genotypes for all the characters. The seed yield per plant exhibited highly significant and positive correlation with number of pods per plant, biological yield per plant, harvest index, number of seeds per pod and pod length. The characteristics such as biological yield per plant, harvest index, number of pods per plant, pod length, number of seeds per pod, plant height, 100-seed weight and days to 50 per cent flowering had high positive direct effect on seed yield per plant. Therefore, selection based on the traits viz., number of pods per plant, biological yield per plant, harvest index, number of seeds per pod, 100-seed weight and pod length could help in enhancing the seed yield per plant in mungbean.

Exploring GGE biplot, stability index, correlation, and clustering analysis for growth and seed yield-related traits in celery (Apium graveolens L.)

The effect of genotype by environment interaction is one of the limiting factor for successfully identifying superior genotypes in plant breeding programs. The study aimed to identify celery genotypes with high and stable yields across different environments by assessing genotype-environment (GE) interactions, stability indices, and associations between agronomic parameters. Twenty celery genotypes were sown in randomized complete block design field trials at three locations in Punjab, India, viz., Ludhiana, Amritsar, and Gurdaspur during 2018–19, 2019–20, and 2020–21. Phenotypic data for thirteen agronomic parameters were collected for GE interactions study. The investigation mainly focused on the significance of GGE biplots in explaining GE interactions based on seed yield-related traits. Results revealed significant differences in genotypes, locations, years, and interactions in the studied traits. The WAASB (weighted average of absolute sScores) stability index estimation was highlighted to identify superior genotypes with maximum seed yield and high stability. The investigation specified the suitability of MTSI (multi-trait stability index), which considers multiple traits through genotype-ideotype distance, for assessing stability. Seed yield showed a positive and significant correlation with primary branches and umbels per plant that would be effective in simultaneous selection for multiple traits. Based on MTSI, three genotypes, PAU1, PAU9, and PAU10, were identified as stable and high-yielding across all three tested locations. The investigation suggests that efforts should focus on identifying location-specific genotypes using multi-location and multi-year data for varietal releases rather than emphasizing the overall performance of genotypes.

Association study of the Taq1D rs1800498 polymorphism of the DRD2 gene with personality traits in a group of athletes

Introduction: This study investigates an association between the human dopamine receptor 2 gene DRD2 Taq1D rs1800498 polymorphism and personality traits among athletes, exploring the genetic underpinnings of sports performance and psychological characteristics. It aims to understand how genetic factors related to dopamine reception influence athletic predispositions and behaviors. Materials and Methods: An association study was conducted with 391 male participants, comparing 159 sports subjects with 232 non-trained controls. Personality traits were assessed using the NEO Five-Factor Inventory, while the DRD2 Taq1D rs1800498 polymorphism was genotyped through real-time PCR. Results: Significant differences in the DRD2 Taq1D rs1800498 genotype and allele frequencies were found between athletes and controls, with athletes displaying higher scores in extraversion and conscientiousness on the NEO-FFI scales. These findings suggest a genetic influence on certain personality traits relevant to sports performance. Conclusions: The study supports the notion that genetic factors, specifically the DRD2 Taq1D rs1800498 polymorphism, are associated with personality traits that may influence athletic performance. This insight contributes to the field of psychogenetics in sports, offering a deeper understanding of how genetics and personality interact to shape athletic capabilities.

Hybrid capture-based next-generation sequencing of new and old world Orthohantavirus strains and wild-type Puumala isolates from humans and bank voles

Orthohantaviruses, transmitted primarily by rodents, cause hemorrhagic fever with renal syndrome (HFRS) in Eurasia and hantavirus pulmonary syndrome in the Americas. These viruses, with documented human-to-human transmission, exhibit a wide case-fatality rate, 0.5–40 %, depending on the virus species, and no vaccine or effective treatment for severe Orthohantavirus infections exists. In Europe, the Puumala virus (PUUV), carried by the bank vole Myodes glareolus, causes a milder form of HFRS. Despite the reliance on serology and PCR for diagnosis, the three genomic segments of Swedish wild-type PUUV have yet to be completely sequenced.We have developed a targeted hybrid-capture method aimed at comprehensive genomic sequencing of wild-type PUUV isolates and the identification of other Orthohantaviruses. Our custom-designed panel includes >11,200 probes covering the entire Orthohantavirus genus. Using this panel, we sequenced complete viral genomes from bank vole lung tissue, human plasma samples, and cell-cultured reference strains. Analysis revealed that Swedish PUUV isolates belong to the Northern Scandinavian lineage, with nucleotide diversity ranging from 2.8 % to 3.7 % among them. Notably, no significant genotypic differences were observed between the viral sequences from reservoirs and human cases except in the nonstructural protein.Despite the high endemicity of PUUV in Northern Sweden, these are the first complete Swedish wild-type PUUV genomes and substantially increase our understanding of PUUV evolution and epidemiology. The panel's sensitivity enables genomic sequencing of human samples with viral RNA levels reflecting the natural progression of infection and underscores our panel's diagnostic value, and could help to uncover novel Orthohantavirus transmission routes.

Association of TGFBR2 gene polymorphisms (rs6785358 and rs764522) with congenital heart disease susceptibility in Egyptians

Aim: Transforming growth factor beta (TGF-β) receptor II (TGFBR2) is a basic constituent of TGF-β signalling pathway and is important in heart development. This study investigates the relationship between TGFBR2 gene variance and congenital heart defects (CHD) among Egyptians. Methods: The study involved 75 CHD-affected subjects and 100 healthy controls. Genotyping of two selected tag single nucleotide polymorphisms (tagSNPs, rs6785358, rs764522) within the TGFBR2 gene was conducted using polymerase chain reaction-restriction fragment length polymorphism method (PCR-RFLP) assays. Results: Significant genotype differences were found for rs764522 and rs6785358 (P &lt; 0.05). In the case of rs6785358, the G/G genotype was more prevalent in cases than controls (18.7% vs. 4.0%). This significance was observed in both the codominant model [A/A vs. A/G vs. G/G; odds ratio (OR) = 0.20, 95% confidence interval (CI) = 0.06–0.66, P = 0.0073] and the recessive model (A/A + A/G vs. G/G; OR = 0.19, 95% CI = 0.06–0.60, P = 0.0018). For rs764522, the G/G genotype was more prevalent in cases than controls (21.3% vs. 0.0%). Significant associations were observed in the codominant model (C/C vs. C/G vs. G/G; OR = 0.43, 95% CI = 0.02–0.90, P &lt; 0.0001), as well as in the dominant model (C/C vs. C/G + G/G) and recessive model (C/C + C/G vs. G/G; P &lt; 0.0001). Gender-specific analysis indicated that the C/G genotype was less common in male cases compared to females and controls (OR = 0.24, 95% CI = 0.07–0.84). For rs6785358, the G/G genotype frequency was higher in male cases compared to females and controls (OR = 0.10, 95% CI = 0.01–0.88 and OR = 0.22, 95% CI = 0.05–0.94, respectively). Conclusions: These findings indicate that TGFBR2 gene SNPs (rs6785358 and rs764522) may be risk factors for CHD in Egyptians.

Comparison of Glecaprevir/Pibrentasvir and Sofosbuvir/Ledipasvir in Patients with Hepatitis C Virus Genotype 1 and 2 in South Korea.

This study compared the effectiveness and safety of glecaprevir/pibrentasvir (GLE/PIB) and sofosbuvir/ledipasvir (SOF/LDV) in real-life clinical practice. The data from genotype 1 or 2 chronic hepatitis C patients treated with GLE/PIB or sofosbuvir + ribavirin or SOF/LDV in South Korea were collected retrospectively. The analysis included the treatment completion rate, sustained virologic response at 12 weeks (SVR12) test rate, treatment effectiveness, and adverse events. Seven hundred and eighty-two patients with genotype 1 or 2 chronic hepatitis C who were treated with GLE/PIB (n=575) or SOF/LDV (n=207) were included in this retrospective study. The baseline demographic and clinical characteristics revealed significant statistical differences in age, genotype, ascites, liver cirrhosis, and hepatocellular carcinoma between the GLE/PIB and SOF/LDV groups. Twenty-two patients did not complete the treatment protocol. The treatment completion rate was high for both regimens without statistical significance (97.7% vs. 95.7%, p=0.08). The overall SVR12 of intention-to-treat analysis was 81.2% vs. 80.7% without statistical significance (p=0.87). The overall SVR12 of per protocol analysis was 98.7% vs. 100% without statistical significance (p=0.14). Six patients treated with GLE/PIB experienced treatment failure. They were all male, genotype 2, and showed a negative hepatitis C virus RNA level at the end of treatment. Two patients treated with GLE/PIB stopped medication because of fever and abdominal discomfort. Both regimens had similar treatment completion rates, effectiveness, and safety profiles. Therefore, the SOF/LDV regimen can also be considered a viable DAA for the treatment of patients with genotype 1 or 2 chronic hepatitis C.

Genetic Divergence of Ashwagandha (Withania somnifera (L.) Dunal) for Growth and Yield Traits

Genetic divergence among 32 Ashwagandha (Withania somnifera (L.) Dunal) accessions of different geographic origins was assessed using Mahalanobis D2 statistics. Observations revealed significant genotypic differences, and accordingly, genotypes were classified into six clusters. Cluster I was the largest, with twenty genotypes, followed by the cluster II, which has eight, and clusters III, IV, V, and VI contained only one most divergent genotype. The maximum divergence was observed between clusters II and III (D2 = 47.90), followed by clusters V and VI (D2 = 43.95), and clusters III and VI (D2 = 42.29). Cluster IV had the least inter-cluster distance (D2 = 22.82) with cluster VI. Clusters III, IV, V, and VI had only one genotype each, and hence, the intra-cluster distance was zero. The genotype of cluster V was unique as it had the highest values for fresh and dry root weight per plant, diameter and length of the main root, number of secondary roots per plant, number of berries per plant, and girth of stem with a high seed yield per plant. Cluster VI was desirable in respect of days to 50 per cent flowering and days to root harvest. Cluster II exhibited the highest value for height of plant and branches per plant. Cluster IV had the highest mean values for the number of seeds per berry. Thus, hybridization among these genotypes can generate desirable transgressive segregants. Aim of Studies: To assess the genetic divergen of Withania somnifera. Place and Duration of Study: Department of Horticulture, College of Agriculture, UAS, GKVK, Bengaluru from 2020-21 to 2021-22. Methodology: The genetic divergence between the genotypes in the population was estimated using formula D2= p (Yit - Yjt) and genetic divergence among 32 Ashwagandha (Withania somnifera (L.) Dunal) accessions of different geographic origins was assessed using Mahalanobis D2 statistics. Observations revealed significant genotypic differences, and accordingly. Results: Observations revealed significant genotypic differences, and accordingly, genotypes were classified into six clusters. Cluster I was the largest, with twenty genotypes, followed by the cluster II, which has eight, and clusters III, IV, V, and VI contained only one most divergent genotype. The maximum divergence was observed between clusters II and III (D2 = 47.90), followed by clusters V and VI (D2 = 43.95), and clusters III and VI (D2 = 42.29). Cluster IV had the least inter-cluster distance (D2 = 22.82) with cluster VI. Clusters III, IV, V, and VI had only one genotype each, and hence, the intra-cluster distance was zero. The genotype of cluster V was unique as it had the highest values for fresh and dry root weight per plant, diameter and length of the main root, number of secondary roots per plant, number of berries per plant, and girth of stem with a high seed yield per plant. Cluster VI was desirable in respect of days to 50 per cent flowering and days to root harvest. Cluster II exhibited the highest value for height of plant and branches per plant. Cluster IV had the highest mean values for the number of seeds per berry Conclusion of finding: Significant genetic divergence and complementarity for most features has been shown by the genotypes of clusters II and III and clusters V and VI. This could lead to significant genetic improvement for particular characters and their selection for new varieties.

Distribution patterns of molecular markers of antimalarial drug resistance in Plasmodium falciparum isolates on the Thai-Myanmar border during the periods of 1993–1998 and 2002–2008

BackgroundPolymorphisms of Plasmodium falciparum chloroquine resistance transporter (pfcrt), Plasmodium falciparum multi-drug resistance 1 (pfmdr1) and Plasmodium falciparum kelch 13-propeller (pfk13) genes are accepted as valid molecular markers of quinoline antimalarials and artemisinins. This study investigated the distribution patterns of these genes in P. falciparum isolates from the areas along the Thai-Myanmar border during the two different periods of antimalarial usage in Thailand.ResultsPolymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) were used to detect pfcrt mutations at codons 76, 220, 271, 326, 356, and 371 as well as pfmdr1 mutation at codon 86. The prevalence of pfcrt mutations was markedly high (96.4–99.7%) in samples collected during both periods. The proportions of mutant genotypes (number of mutant/total isolate) at codons 76, 220, 271, 326, 356 and 371 in the isolates collected during 1993–1998 (period 1) compared with 2002–2008 (period 2) were 97.9% (137/140) vs. 97.1% (401/413), 97.9% (140/143) vs. 98.8% (171/173), 97.2% (139/143) vs. 97.1% (333/343), 98.6% (140/142) vs. 99.7% (385/386), 96.4% (134/139) vs. 98.2% (378/385) and 97.8% (136/139) vs. 98.9% (375/379), respectively. Most isolates carried pfmdr1 wild-type at codon 86, with a significant difference in proportions genotypes (number of wild type/total sample) in samples collected during period 1 [92.9% (130/140)] compared with period 2 [96.9% (379/391)]. Investigation of pfmdr1 copy number was performed by real-time PCR. The proportions of isolates carried 1, 2, 3 and 4 or more than 4 copies of pfmdr1 (number of isolates carried correspondent copy number/total isolate) were significantly different between the two sample collecting periods (65.7% (90/137) vs. 87.8% (390/444), 18.2% (25/137) vs. 6.3%(28/444), 5.1% (7/137) vs. 1.4% (6/444) and 11.0% (15/137) vs. 4.5% (20/444), for period 1 vs. period 2, respectively). No pfk13 mutation was detected by nested PCR and nucleotide sequencing in all samples with successful analysis (n = 68).ConclusionsThe persistence of pfcrt mutations and pfmdr1 wild-types at codon 86, along with gene amplification in P. falciparum, contributes to the continued resistance of chloroquine and mefloquine in P. falciparum isolates in the study area. Regular surveillance of antimalarial drug resistance in P. falciparum, incorporating relevant molecular markers and treatment efficacy assessments, should be conducted.

HOMER1 Polymorphism and Parkinson's Disease-Psychosis: Is there an Association?

Homer1, a postsynaptic protein coded by the HOMER1 gene, presumably has a role in homeostatic plasticity that dampens neuronal responsiveness when the input activity is too high. HOMER1 polymorphism has been studied in major psychiatric disorders such as schizophrenia. The objective of this study is to investigate if polymorphisms of the HOMER1 gene are associated with psychosis in Parkinson's disease (PD-P). One hundred patients with Parkinson's disease (PD) and 100 healthy controls were enrolled consecutively in a PD-P biomarker study at the National Institute of Mental Health and Neurosciences, Bangalore, India. Of the 100 PD patients, 50 had psychosis (PD-P) and 50 did not have psychosis (PD-NP). Two single-nucleotide polymorphisms of HOMER1 (rs4704559 and rs4704560) were analyzed from the DNA isolated from peripheral blood. The allele and genotype frequencies in the PD-P and PD-NP groups were compared. Analysis of HOMER1 rs4704560 revealed a significant difference in both genotype and allele levels between PD-P and PD-NP groups. There was an overrepresentation of T-allele (42% vs. 16%; P < 0.001) and TT genotype (24% vs. 6%; P < 0.001) in the PD-P group compared to PD-NP group. There was no significant difference between PD-P and PD-NP groups when various genotypes and allele frequencies related to HOMER1 rs4704559 were compared. PD-P is probably associated with overrepresentation of T-allele of HOMER1 rs4704560, and larger studies are warranted to confirm our results.

Effects of Cd Stress on Morphological and Physiological Characteristics of Maize Seedlings

Heavy metal (HM) contamination poses a serious threat to safe crop production and human health, and different maize inbred lines respond differently to cadmium (Cd) stress. However, the morphological and physiological characteristics of maize inbred lines seedlings are not clear under Cd stress. In this study, we analyzed the agronomic traits and physiological and biochemical indices of inbred maize seedlings under Cd stress in the seedling stage using the inbred lines Kui3, CML118, Mo17, B73, and B77 as the materials. These five inbred maizes were treated with five different concentrations of Cd (0, 1, 3, 5, and 7 mg L−1, respectively) were applied and the indices of the maize seedlings determined on day 15. The aboveground and belowground biomass of five maize inbred lines seedlings showed a decreasing trend under Cd stress. Leaf relative water content and SPAD values also decreased, but the overall decrease in relative water content was small, and the differences were not significant. Surprisingly, Cd stress affected the activities of superoxide dismutase (SOD), peroxidase (POD), and catalase (CAT), leading to enhanced mem-brane lipid peroxidation. The cadmium content varied greatly between varieties under Cd stress, but all of them had lower Cd content above ground than below ground, and the varieties with the highest and lowest transfer coefficients were Mo17 (0.33–0.83) and B73 (0.06–0.44), respectively. Kui3 had the greatest difference in soluble protein content under Cd stress, which showed a de-creasing trend, and the soluble sugar content was significantly decreased in general compared to that of CK. The soluble sugar content was higher than CK under Cd treatment, and the proline content of the maize seedlings of all of the inbred lines showed an increasing trend compared to CK. Overall, there were significant genotypic differences in the Cd stress response to Cd toxicity in the maize inbred lines seedlings, and, in general, this study helps us to understand the mechanism of maize inbred lines seedlings response to Cd stress. It provides a theoretical basis for the se-lection and breeding of varieties, and food safety.

Genetic evaluation of hulless barley (Hordeum vulgare) genotypes for morpho-physiological traits and stripe rust resistance

Nowadays, hulless barley (Hordeum vulgare L.) is gaining importance as a raw material for food industry due to its highly nutritive value. Non-availability of high yield and disease resistant varieties has restricted its production in marginal areas over the last two decades. Therefore, an experiment was conducted during 2017–18 and 2018–19 at the Seed and Research Farm of ICAR-Indian Institute of Wheat and Barley Research, Karnal, Haryana to characterized 11 exotic hulless barley genotypes and 4 Indian barley cultivars for morpho-physiological characters and stripe rust resistance. Seedling resistant test for stripe rust was done at Regional Station (ICAR-Indian Institute of Wheat and Barley Research), Flowerdale, Shimla, Himachal Pradesh. Highly significant genotypic differences were found for morpho-physiological traits during analysis of variance. Genotype DWRNB28 showed a good combination of desirable traits, viz. early maturity (118 days), dwarf plant height (64.4 cm) and high 1000-grain weight (55.2 g). Maximum number of tillers per meter (149) was observed in DWRNB17. Genotype DWRNB25 was found resistant to maximum pathotypes (6S0, 7S0, and Q) at the seedling stage. DWRNB23 and DWRNB25 with pooled ACI=0 and ACI=0.04 respectively, were found immune to stripe rust in field conditions. These promising genotypes can be utilized as donor parents for the development of high-yielding and stripe-rust-resistant hulless barley varieties.

Polymorphic Variants of SCN5A Gene (rs41312433 and rs1805124) Associated with Coronary Artery Affliction in Patients with Severe Arrhythmias.

A group of 32 unrelated individuals, aged 63 ± 12 years, was included in the study. All the patients were examined, diagnosed and treated with an implantable cardioverter defibrillator at the Department of Internal Cardiology Medicine, Faculty Hospital Brno. The control group included 87 persons of similar age without afflicted coronary circulation, which was confirmed coronagraphically. Genomic DNA was extracted from samples of peripheral blood according to the standard protocol. Two SCN5A polymorphisms-IVS9-3C/A (rs41312433) and A1673G (rs1805124, H558R)-were examined in association with coronary artery stenosis in the patients. In the case-control study, no significant differences in genotype distribution/allelic frequencies were observed for IVS9-3c>a and A1673G gene polymorphisms between patients with severe arrhythmias and healthy persons. The distribution of SCN5A double genotypes was not significantly different among different types of arrhythmias according to their ejection fraction in arrhythmic patients (p = 0.396). The ventricular arrhythmias with an ejection fraction below 40% were found to be 10.67 times more frequent in patients with multiple coronary stenosis with clinically valid sensitivity, specificity and power tests. In the genotype-phenotype study, we observed a significant association of both SCN5A polymorphisms with the stenosis of coronary vessels in the patients with severe arrhythmia. The double genotype of polymorphisms IVS9-3C/A together with A1673G (CCAA) as well as their simple genotypes were associated with significant multiple stenosis of coronary arteries (MVS) with high sensitivity and specificity (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.70; specificity 0.682; power test 0.359) Moreover, when a concrete stenotic coronary artery was associated with SCN5A genotypes, the CCAA double genotype was observed to be five times more frequent in patients with significant stenosis in the right coronary artery (RCA) compared to those without affliction of this coronary artery (p = 0.05; OR = 5 (95% CI 0.99-23.34); sensitivity 0.682; specificity 0.700; power test 0.359). The CCAA genotype was also more frequent in patients without RCA affliction with MVS (p = 0.008); in patients with ACD affliction but without MVS (p = 0.008); and in patients with both ACD affliction and MVS compared to those without ACD affliction and MVS (p = 0.005). Our study presents a highly sensitive and specific association of two polymorphisms in SCN5A with significant coronary artery stenoses in patients with potentially fatal ventricular arrhythmias. At the same time, these polymorphisms were not associated with arrhythmias themselves. Thus, SCN5A gene polymorphic variants may form a part of germ cell gene predisposition to ischemia.

Genotypic Differences in Morphological, Physiological and Agronomic Traits in Wheat (Triticum aestivum L.) in Response to Drought.

Drought is one of the main environmental factors affecting crop growth, and breeding drought-tolerant cultivars is one of the most economic and effective ways of increasing yields and ensuring sustainable agricultural production under drought stress. To facilitate the breeding of drought-tolerant wheat, this study was conducted to evaluate genotypic differences in the drought tolerance of 334 wheat genotypes collected from China and Australia with the aim of screening for drought-tolerant and -sensitive genotypes and to elucidate the corresponding physiological mechanisms. A hydroponic-air experiment (roots exposed to air for 7 h/d and continued for 6 d) showed significant genotypic differences in shoot and root dry weights among the genotypes. The relative shoot and root dry weights, expressed as the percentage of the control, showed a normal distribution, with variation ranges of 20.2-79.7% and 32.8-135.2%, respectively. The coefficients of variation were in the range of 18.2-22.7%, and the diversity index was between 5.71 and 5.73, indicating a rich genetic diversity among the wheat genotypes for drought tolerance. Using phenotypic differences in relative dry weights in responses to drought stress, 20 of each of the most drought-tolerant and drought-sensitive genotypes were selected; these were further evaluated in pot experiments (watering withheld until the soil moisture content reached four percent). The results showed that the trends in drought tolerance were consistent with the hydroponic-air experiment, with genotypes W147 and W235 being the most drought-tolerant and W201 and W282 the most sensitive. Significant genotypic differences in water use efficiency in response to drought were observed in the pot experiment, with the drought-tolerant genotypes being markedly higher and the two sensitive genotypes being no different from the control. A marked increase in bound water content in the drought stress plants was observed in the two drought-tolerant genotypes, while a decrease occurred in the free water. The reductions in photochemical efficiencies of PSII, transpiration rates, net photosynthesis rates, chlorophyll contents and stomatal conduction in the drought-sensitive genotypes W201 and W282 under drought stress were higher than the two tolerant genotypes. This study provides a theoretical guide and germplasm for the further genetic improvement of drought tolerance in wheat.

Evaluation of the participation of ABCA1 transporter in epicardial and mediastinal adipose tissue from patients with coronary artery disease.

Recent studies have shown a relationship between adipose tissue and coronary artery disease (CAD). The ABCA1 transporter regulates cellular cholesterol content and reverses cholesterol transport. The aim of this study was to determine the relationship between single nucleotide polymorphisms (SNPs) R230C, C-17G, and C-69T and their expression in epicardial and mediastinal adipose tissue in Mexican patients with CAD. The study included 71 patients with CAD and a control group consisting of 64 patients who underwent heart valve replacement. SNPs were determined using TaqMan probes. mRNA was extracted using TriPure Isolation from epicardial and mediastinal adipose tissue. Quantification and expression analyses were done using RT-qPCR. R230C showed a higher frequency of the GG genotype in the CAD group (70.4%) than the control group (57.8%) [OR 0.34, 95% CI (0.14-0.82) p = 0.014]. Similarly, C-17G (rs2740483) showed a statistically significant difference in the CC genotype in the CAD group (63.3%) in comparison to the controls (28.1%) [OR 4.42, 95% CI (2.13-9.16), p = 0.001]. mRNA expression in SNP R230C showed statistically significant overexpression in the AA genotype compared to the GG genotype in CAD patients [11.01 (4.31-15.24) vs. 3.86 (2.47-12.50), p = 0.015]. The results suggest that the GG genotype of R230C and CC genotype of C-17G are strongly associated with the development of CAD in Mexican patients. In addition, under-expression of mRNA in the GG genotype in R230C is associated with patients undergoing revascularization.