Genotype Combinations Research Articles

Genetic Associations of Plasminogen Activator Inhibitor-1-Related miRNA Variants with Coronary Artery Disease

Coronary artery disease (CAD) is one of the most common types of cardiovascular disease and can lead to a heart attack as plaque gradually builds up inside the coronary arteries, blocking blood flow. Previous studies have shown that polymorphisms in the PAI-1 gene are associated with CAD; however, studies of the PAI-1 3′-untranslated region, containing a miRNA binding site, and the miRNAs that interact with it, are insufficient. To investigate the association between miRNA polymorphisms and CAD in the Korean population based on post-transcriptional regulation, we genotyped five polymorphisms in four miRNAs targeting the 3′-untranslated region of PAI-1 using real-time PCR and TaqMan assays. We found that the mutant genotype of miR-30c rs928508 A > G was strongly associated with increased CAD susceptibility. In a genotype combination analysis, the combination of the homozygous mutant genotype (GG) of miR-30c rs928508 with the wild-type genotype (GG) of miR-143 rs41291957 resulted in increased risk for CAD. Also, in an allele combination analysis, the combination of the mutant allele (G) of miR-30c rs928508 and the wild-type allele (G) of miR-143 rs41291957 resulted in increased risk for CAD. Furthermore, metabolic syndrome and diabetes mellitus showed synergistic effects on CAD risk when combined with miR-30c rs928508. These results can be applied to identify CAD prognostic biomarkers among miRNA polymorphisms and various clinical factors.

Characterization of the myostatin gene in the neotropical species Piaractus mesopotamicus and the possibility of its use in genetic improvement programs.

The myostatin gene has played an important role in the genetic improvement of the main species of economic importance; however, it has not yet been described for some Neotropical fish essential for aquaculture. This study aimed to characterize the myostatin gene of pacu, Piaractus mesopotamicus, and investigate the association of a microsatellite marker in this gene with the weight of fish. The myostatin gene sequence was obtained after following a RACE-PCR strategy based on a partial mRNA sequence available in the GenBank database and the alignment of myostatin sequences from other fish species. The obtained sequence for the P. mesopotamicus gene was analyzed for short tandem repeats, and one dinucleotide was observed at the 3´untranslated region. A short tandem repeat polymorphism was verified in a wild population. Subsequently, the STR was evaluated in a test population of 232 animals in two 220m² concrete tanks at the Aquaculture Center of Unesp. Eight alleles and 22 genotype combinations were identified. A significant association was observed between microsatellite marker polymorphisms and the weight traits (WEIGHT1 and WEIGHT2). Alleles 210, 222, 226, and 230 were found to favor weight gain. In summary, this study contributes to the characterization of the myostatin gene in pacu fish and identifies an association between a STR and weight traits. Thus, this gene could be used as a target for genetic breeding using molecular strategies such as CRISPR and quantitative strategies such as marker-assisted selection, which would contribute to improving the production of the species.

Host genetics shapes Pinus radiata phenotypic plasticity under drought and is linked with root-associated soil microbiome shifts

Under current and future climate scenarios, identifying drought-resistant tree species, tree genotypes, and beneficial interactions between trees and their root-associated soil microbiomes is becoming more imperative for maintaining tree health and sustaining increasingly vulnerable forests. We designed a genotype x soil x watering x time glasshouse experiment using Pinus radiata as a model tree to assess the magnitude of the effect of host genotype and root-associated soil microbiome on the phenotype response (functional traits, metabolome, nutrients) under drought. We identified the shikimate pathway as a critical metabolic pathway for Pinus radiata drought resistance, with the shikimic acid intermediate being one of the strongest drought signals, besides downstream metabolites such as flavonoids and phenylpropanoids. Overall, we found that the host genotype diversity was a key actor in the observed phenotype response of P. radiata to drought. In contrast, the microbiome was attributed a minor supporting role. Contrary to our hypothesis, dry soils could not support drought-sensitive genotypes under drought stress. Instead, the drought-resistant genotype was able to leverage locally adaptive bacteria to match local selective drought pressures at the expense of tree growth. This highlights the significance of finding specific combinations of tree genotype and mutualistic microbial communities that would thrive under future environmental pressures.

Polymorphisms of PRKAA1 and FABP4 genes and their association with feed efficiency in Hu sheep

Feed efficiency (FE) is an important economic trait in the sheep industry, influenced by biological processes such as digestion and metabolism. PRKAA1 gene participates in the synthesis and oxidation of fatty acids; the FABP4 gene is closely associated with intracellular fatty acid regulation. In this study, we use Sanger sequencing, KASPar genotyping, and qRT-PCR to investigate the association between variations in PRKAA1 and FABP4 genes and feed efficiency in Hu sheep, the expression patterns of PRKAA1 and FABP4 genes in different tissues, as well as the differences in expression of different genotypes in tail fat. The association analysis results indicated that PRKAA1 gene g.35431965 C > T locus and FABP4 gene g.62829807 C > T locus were significantly associated with the feed conversion ratio (FCR) of Hu sheep aged 80–180 days, with the dominant genotypes being CC and CC, respectively. Simultaneously, there existed notable disparities among various genotype combinations. The qRT-PCR results showed PRKAA1 and FABP4 genes were widely expressed in ten tissues, of which the PRKAA1 gene was lower expression level in rumen and lung, FABP4 gene was significantly highest expression in the tail fat than the other tissues; the expression of two different genotypes in tail fat also exhibits significant differences (P ≤ 0.05). Therefore, these findings suggested that the variation of PRKAA1 and FABP4 genes might be used as novel genetic marker for improving feed efficiency in sheep.

Unusual BA222-like strains of Rotavirus A (Sedoreoviridae: Rotavirus: Rotavirus A): molecular and genetic analysis based on all genome segments.

Rotavirus infection is the major cause of severe dehydrating diarrhea requiring hospitalization in young children worldwide. Due to their segmented genome, rotaviruses are capable of gene reassortment, which makes the emergence and spread of genetically novel strains possible. The purpose of this study was to search for unusual rotaviruses circulating in Nizhny Novgorod in 2021‒2023 and their molecular genetic characterization based on all genome segments. Rotavirus-positive stool samples of children were examined by PCR genotyping and electrophoresis in PAAG. cDNA fragments of each of the 11 genes (VP1‒VP4, VP6, VP7, NSP1‒NSP5), 570 to 850 nucleotide pairs in length were sequenced for the selected strains. The phylogenetic analysis was performed in the MEGA X program. In the study period 2021‒2023, 11 G[P] combinations with a predominance of G3P[8] (59.5%) were identified. Six atypical Rotavirus А (RVA) strains were identified: 2 strains of the G2P[4] genotype (G2-P[4]-I2-R2-C2-M2-A3-N2-T3-E2-H3, G2-P[4]-I2-R2-C2-M2-A3-N2-T3-E3-H2) and 4 G3P[9] strains (all strains had the genotype G3-P[9]-I2-R2-C2-M2-A3-N2-T3-E3-H3). Phylogenetic analysis based on all genes showed an evolutionary relationship between rotaviruses similar to rotaviruses of cats and dogs (BA222-like) and unusual strains of the G2P[4] genotype, for which a mixed combination of genotypes was identified and characterized for the first time. The results obtained expand the understanding of the diversity of reassortant RVAs, as well as complement the data on the genotypic structure of the rotavirus population in Nizhny Novgorod. The wide genetic diversity of reassortant RVA can help rotaviruses overcome the immunological pressure provided by natural and vaccine-induced immunity. In this regard, to control the emergence of new variants and assess changes in the virulence of rotaviruses after reassortment processes, continuous molecular monitoring for circulating RVA is necessary.

Influence of different genotype combinations of β-lactoglobulin and β-casein in cow milk on physicochemical and sensory properties of stirred yoghurt

In this study, stirred yoghurts were produced from Turkish Holstein cow milk with different genotype combinations of β-lactoglobulin and β-casein. The distribution of AA, AB, and BB genotypes of β-lactoglobulin and A1A1, A1A2, and A2A2 genotypes of β-casein was determined in a total of 135 cow milk samples. Raw cow milk samples containing AA genotype of β-LG exhibited higher non-fat total solids, protein, and fat contents in comparison to milk containing AB and BB genotypes of β-LG. Compared to the samples made from milk with other β-LG genotypes, the stirred yoghurt made from milk with β-LG AA genotype showed lower degree of syneresis and higher for hardness, apparent viscosity, and consistency coefficient. The lowest number of grains, the perimeter of grains, and the visual roughness values were obtained in the stirred yoghurts made from milk with BB genotype of β-LG and A2A2 genotype of β-CN. The sensory analysis revealed that β-CN genotypes of milk significantly influenced the overall acceptability scores of the stirred yoghurts, while β-LG genotypes did not significantly influence these scores except for the visual grainy score. The findings of this study showed that the selection of specific milk protein genotypes resulted in substantial differences in the physicochemical and sensory properties of stirred yoghurt.

A phenome-wide association study of methylated GC-rich repeats identifies a GCC repeat expansion in AFF3 associated with intellectual disability.

GC-rich tandem repeat expansions (TREs) are often associated with DNA methylation, gene silencing and folate-sensitive fragile sites, and underlie several congenital and late-onset disorders. Through a combination of DNA-methylation profiling and tandem repeat genotyping, we identified 24 methylated TREs and investigated their effects on human traits using phenome-wide association studies in 168,641 individuals from the UK Biobank, identifying 156 significant TRE-trait associations involving 17 different TREs. Of these, a GCC expansion in the promoter of AFF3 was associated with a 2.4-fold reduced probability of completing secondary education, an effect size comparable to several recurrent pathogenic microdeletions. In a cohort of 6,371 probands with neurodevelopmental problems of suspected genetic etiology, we observed a significant enrichment of AFF3 expansions compared with controls. With a population prevalence that is at least fivefold higher than the TRE that causes fragile X syndrome, AFF3 expansions represent a major cause of neurodevelopmental delay.

Influence of COMT (rs4680) and OPRM1 (rs1799971) on Cancer Pain, Opioid Dose, and Adverse Effects.

Background: The influence of pharmacogenomics on opioid response, particularly with COMT (rs4680) and OPRM1 (rs1799971) variants, has been studied individually and in combination. However, most studies are in a noncancer context and not all their possible variant combinations have been examined. Objectives: This study examined COMT (rs4680) and OPRM1 (rs1799971), and their allele combinations, in advanced cancer to examine associations with pain scores, opioid dose, and adverse effects. Setting/Subjects: This multicenter prospective cohort study recruited patients receiving opioids for advanced cancer pain in Melbourne, Australia. Clinical data (demographics, opioids), validated instruments (pain and adverse effects), and blood (DNA) were collected. Descriptive analyses were used. Univariate and multivariate logistic regression analyses were used to evaluate associations between clinical outcomes (opioid dose, pain, adverse effects) and genotypes of interest. Results: Fifty-four participants were recruited to the study. Those with COMT A allele required lower opioid doses [130 mg (interquartile range [IQR] 67.5,230) versus 180 mg (IQR 55,322.5), p = 0.047] and experienced greater adverse effects [sickness response aOR (adjusted odds ratio) 7.1 (95% CI 1.51,33.41), p = 0.01]. Those with the COMT GG/OPRM1 G allele combination required higher opioid doses [322.5 mg (IQR 264,360) versus 125 mg (65,225), (p = 0.04)]. Those with COMT AG/OPRM1 AA experienced higher average pain [aOR 1.55 (95% CI 1.03, 2.33), p = 0.04] and moderate-severe nausea [aOR 5.47 (95% CI 1.35, 22.21), p = 0.02] but reduced drowsiness [aOR 0.25 (95% CI 0.06, 1.02), p = 0.05]. Conclusions: Patients with cancer with the COMT alternate (A) allele have greater sickness response adverse effects, which may be responsible for the lower opioid doses observed. Significant results of two new COMT/OPRM1 genotype combinations are presented that have not previously been studied, with plausible phenotype descriptions suggested.

Milletomics: a metabolomics centered integrated omics approach toward genetic progression.

Producing alternative staple foods like millet will be essential to feeding ten billion people by 2050. The increased demand for millet is driving researchers to improve its genetic variation. Millets include protein, dietary fiber, phenolic substances, and flavonoid components. Its climate resilience makes millet an appealing crop for agronomic sustainability. Integrative omics technologies could potentially identify and develop millets with desirable phenotypes that may have high agronomic value. Millets' salinity and drought tolerance have been enhanced using transcriptomics. In foxtail, finger, and pearl millet, proteomics has discovered salt-tolerant protein, phytohormone-focused protein, and drought tolerance. Metabolomics studies have revealed that certain metabolic pathways including those involving lignin, flavonoids, phenylpropanoid, and lysophospholipids are critical for many processes, including seed germination, photosynthesis, energy metabolism, and the synthesis of bioactive chemicals necessary for drought tolerance. Metabolomics integration with other omics revealed metabolome engineering and trait-specific metabolite creation. Integrated metabolomics and ionomics are still in the development stage, but they could potentially assist in comprehending the pathway of ionomers to control nutrient levels and biofortify millet. Epigenomic analysis has shown alterations in DNA methylation patterns and chromatin structure in foxtail and pearl millets in response to abiotic stress. Whole-genome sequencing utilizing next-generation sequencing is the most proficient method for finding stress-induced phytoconstituent genes. New genome sequencing enables novel biotechnological interventions including genome-wide association, mutation-based research, and other omics approaches. Millets can breed more effectively by employing next-generation sequencing and genotyping by sequencing, which may mitigate climate change. Millet marker-assisted breeding has advanced with high-throughput markers and combined genotyping technologies.

MTOR gene variant rs2295080 might be a risk factor for atherosclerosis in Iranian women with type 2 diabetes mellitus

BackgroundType 2 diabetes mellitus, one of the most prevalent metabolic disorders worldwide, is closely linked with an enhanced risk of atherosclerosis. However, the molecular mechanism of this linkage is not still clear. Genetic variations in the mTOR gene may increase the susceptibility of individuals to these diseases.MethodsOne hundred nine diabetic patients and 375 healthy subjects participated in this study. mTOR Single Nucleotide Polymorphism (SNP) rs2295080 was determined using Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-RFLP).ResultsComparison of genotypic, allelic, and genotypic combination frequencies between cases and controls revealed no significant result. Nevertheless, the frequency of rs2295080 GT + TT genotype was significantly more in diabetic women with atherosclerosis compared with those without atherosclerosis (p = 0.047). Besides, the rs2295080 G allele was more frequently detected in diabetic women without atherosclerosis compared to those with atherosclerosis (p = 0.046).ConclusionThe rs2295080 GT + TT genotype predisposes Iranian diabetic women to atherosclerosis, while the rs2295080 G allele protects them against atherosclerosis. However, additional experiments using larger sample sizes are needed to verify this result.

HPV infection patterns and viral load distribution: implication on cervical cancer prevention in Western Kenya.

Human papillomavirus (HPV) coinfection remains common globally. However, its clinical significance compared to mono-infection remains controversial. Further, the epidemiology of HPV genotype combination in coinfection is not well studied in Kenya. . Between June and August 2023, a cross-sectional facility-based survey enrolled 434 women aged 16-68 years using purposive sampling strategy. Structured questionnaire was obtained from each woman regarding demographic and sexual behavior characteristics. Cervical specimen was collected from each participant and analyzed using RIATOL assay to determine HPV genotypes and viral load. Overall, HPV 52 was the most frequently detected HPV strain. The mean HPV viral load was elevated among coinfected women than those with mono-infection but there was no evidence to support differences in viral load in the two groups (P = 0.113). Mono-infection was common (58.52%). HPV 16 was noted to have a near equal presence both in mono-infection and coinfection (52.17% and 47. 83%), respectively. HPV 33 (alpha 9) and 45 (alpha 7) had the greatest preference for each other compared to all other HPV interactions. HPV 52 is the most prevalent HPV in the population supporting the need for the nonavalent HPV vaccine. Mono-infection with HPV 16 remains common corroborating the relevance of bivalent vaccine in resource limited setting where nonavalent vaccines may be unavailable. The frequent coinfection preference of HPV 33 and 45 (alpha 9 and alpha 7, respectively) pauses the need for further concurrent characterization. HPV vaccination and education on safe sexual behaviors is key in reducing HPV coinfection.

Association of Polymorphisms in FSHR, ESR1, and BMP15 with Primary Ovarian Insufficiency and Meta-Analysis.

Primary ovarian insufficiency (POI) can lead to menstrual disturbance, resulting in ovarian dysfunction before age 40. Prevalence of POI is usually less than 1%; however, ethnicity or population characteristics may affect prevalence. POI is a heterogeneous disease that results from abnormalities in immunological and hormonal factors. Genetic factors can also contribute to POI. Here, we examine FSHR, ESR1, and BMP15 polymorphisms in patients with POI, and controls. We examined a hormonal gene that is important for pregnancy, follicle-stimulating hormone receptor (FSHR), as well as estrogen receptor 1 (ESR1), and associated it with FSHR expression, ovulation rate, and bone morphogenetic protein 15 (BMP15). We examined 139 Korean patients under age 40 with POI, and 350 Korean control participants without POI. Genotyping was performed by a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) and TaqMan assays. Each identified genotype was subjected to statistical analysis to determine the odds ratios (ORs) and 95% confidence intervals (CIs). In combination genotype analyses, FSHR rs6165 A > G combined with ESR1 rs9340799 A > G, AG/GG (OR: 5.693; 95% CI: 1.088-29.792), as well as FSHR rs6166 A > G combined with ESR1 rs9340799 C > T, AG/GG (OR: 5.940; 95% CI: 1.134-31.131), were significantly associated with POI prevalence. Furthermore, an FSHR rs6165 A > G and BMP rs17003221 C > T, AG/CC combination was associated with POI prevalence (OR: 1.874; 95% CI: (1.059-3.316; p-value: 0.031)). In meta-analysis, FSHR rs6165 AA vs. AG + GG is associated with POI (p = 0.0013), and ESR1 rs2234693 AA vs. AG + GG is also associated with POI (p = 0.0101). Here, we compared the genotypes of FSHR, ESR1, and BMP15 in patients with POI, and controls. We found significant differences in genotype combinations between polymorphisms in FSHR and other genes. Through meta-analysis, we found that ESR1 rs9340799 and rs2234693 are associated with POI prevalence, and that BMP15 rs17003221 increases POI risk. These findings help to improve POI diagnosis in Korean women.

Distribution of CYP3A4 and CYP3A5 Polymorphisms and Genotype Combination Implicated in Tacrolimus Metabolism.

Human cytochrome P450 (CYP), particularly CYP3A4 and CYP3A5 is mainly responsible for the metabolism of several drugs including tacrolimus. Significant interracial/interethnic variation in the expression and function of CYP3A5 and CYP3A4 is caused by Single Nucleotide Polymorphisms (SNPs) of genes encoding these proteins. The present study investigated the genetic polymorphisms CYP3A4*1B, CYP3A4*22, and CYP3A5*3 in the Tunisian population. We included in this study, Tunisian healthy subjects and renal transplant recipients receiving tacrolimus. CYP3A4 and CYP3A5 genotyping were performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). According to the genotypic combination of the three CYP polymorphisms, we have identified for the first time four metabolizers statuses: slow metabolizers (SM), intermediate metabolizers (IM), high metabolizers (HM), and extensive metabolizers (EM). A total of 101 renal transplant patients and 102 healthy subjects were included. Our results showed that the predominant alleles in the Tunisian population are a wild type of CYP3A4*1B (0.87), likewise CYP3A4*22 (0.975) and CYP3A5*3 (0.82). The genotype frequencies of CYP3A4*1B, CYP3A4*22, and CYP3A5*3 were found to be 3.9%, 0.0%, and 69.5%, respectively. Also, we found a significant linkage disequilibrium between CYP3A4*1B and CYP3A5*3. We approved that the IM is the predominant phenotype in our population with 124 patients followed by and EM with 41 patients, HM in 29 patients and SM in 9 patients. These results showed that Tunisians are most similar to Caucasians. The genetic background of these enzymes CYP3A4*1B, CYP3A4*22, and CYP3A5*3 in this study are important in the prescription of personalized medicine.

A Heuristic Approach to Analysis of the Genetic Susceptibility Profile in Patients Affected by Airway Allergies.

Allergic respiratory diseases such as asthma might be considered multifactorial diseases, having a complex pathogenesis that involves environmental factors and the activation of a large set of immune response pathways and mechanisms. In addition, variations in genetic background seem to play a central role. The method developed for the analysis of the complexities, as association rule mining, nowadays may be applied to different research areas including genetic and biological complexities such as atopic airway diseases to identify complex genetic or biological markers and enlighten new diagnostic and therapeutic targets. A total of 308 allergic patients and 205 controls were typed for 13 single nucleotide polymorphisms (SNPs) of cytokine and receptors genes involved in type 1 and type 2 inflammatory response (IL-4 rs2243250 C/T, IL-4R rs1801275A/G, IL-6 rs1800795 G/C, IL-10 rs1800872 A/C and rs1800896 A/G, IL-10RB rs2834167A/G, IL-13 rs1800925 C/T, IL-18 rs187238G/C, IFNγ rs 24030561A/T and IFNγR2 rs2834213G/A), the rs2228137C/T of CD23 receptor gene and rs577912C/T and rs564481C/T of Klotho genes, using KASPar SNP genotyping method. Clinical and laboratory data of patients were analyzed by formal statistic tools and by a data-mining technique-market basket analysis-selecting a minimum threshold of 90% of rule confidence. Formal statistical analyses show that IL-6 rs1800795GG, IL-10RB rs2834167G positive genotypes, IL-13 rs1800925CC, CD23 rs2228137TT Klotho rs564481TT, might be risk factors for allergy. Applying the association rule methodology, we identify 10 genotype combination patterns associated with susceptibility to allergies. Together these data necessitate being confirmed in further studies, indicating that the heuristic approach might be a straightforward and useful tool to find predictive and diagnostic molecular patterns that might be also considered potential therapeutic targets in allergy.

Grafting in Coffea canephora: a strategy to enhance growth and photosynthetic rates for environments with contrasting water availabilities

Water deficit is one of the main limiting factors for the yield in most regions where Coffea canephora is cultivated. This problem has been amplified by the climate changes in recent years. The objective of this work was to study the response of grafting combinations between genotypes of C. canephora, cultivated in contrasting conditions of water availability, and their effects over the initial growth and photosynthetic rates of the plants. For this end, grafted plants with four combinations of genotypes (201/14, 201/RT, 02/14 and 02/RT) were submitted to two contrasting conditions of water supply (80% and 25% of available water in the soil). The initial growth, dry matter accumulation, and leaf gas exchanges were evaluated. Under abundant water supply, the grafting combination 02/RT achieved higher initial growth, whereas 02/14 maintained higher growth under conditions of water deficit. Under adequate water supply, the combinations 201/14 and 201/RT stand out regarding water use parameters, while in conditions of water deficit, the combination 201/14 was capable of keeping higher efficiencies.

Evaluating the evidence for genotype-informed Bayesian dosing of tacrolimus in children undergoing solid organ transplantation: A systematic literature review.

Tacrolimus, a calcineurin inhibitor, is a highly effective immunosuppressant used in solid organ transplantation (SOT). However, it is characterized by a narrow therapeutic range and high inter-patient variability in pharmacokinetics. Standard weight-based dosing followed by empiric dose titration is suboptimal in controlling drug concentrations, increasing risk of rejection or toxicity, particularly in the initial months post transplantation. This review explores the potential of combined pre-transplant genotyping and pharmacokinetic (PK) modelling to improve tacrolimus dosing in paediatric SOT recipients. A systematic search of Medline, Embase and Cochrane databases identified studies published between March 2013 and March 2023 that investigated genotype- and PK model-informed tacrolimus dosing in children post-SOT. The Newcastle-Ottawa Scale assessed study quality. Seven studies encompassing paediatric kidney, heart, liver and lung transplants reported using genotype and model-informed dosing. A combination of clinical and genetic factors significantly impacts tacrolimus clearance and thus initial dose recommendation. Body size, transplant organ and co-medications were consistently important, while either time post-transplant or haematocrit emerged in some studies. Several models were identified, however, with limitations evident in some and with absence of evidence for their effectiveness in optimizing initial and subsequent dosing. This review highlights the development of PK models in paediatric SOT that integrate genotype and clinical covariates to personalize early tacrolimus dosing. While promising, prospective studies are needed to validate and confirm their effectiveness in improving time to therapeutic concentrations and reducing under- or overexposure. This approach has the potential to optimize tacrolimus therapy in paediatric SOT, thereby improving outcomes.

Impact of genotypic mixture on soybean (Glycine max) pest population

An experiment was conducted during rainy (kharif) seasons of 2018 and 2019 at the ICAR-Indian Institute of Soybean Research, Indore, and Madhya Pradesh to study the impact of genotypic mixture on soybean [Glycine max (L.) Merr.] pest population. A total of 16 soybean genotypes and 4 genotypic mixtures were evaluated for relative efficacy in management of insect-pests of soybean. Among the 20 treatments, the plots with genotypic mixtures had lowest population of Spodoptera exigua Hubner and at par with each other. In case of Spodoptera litura Fabricius, tussock moth, blue beetle and grey weevil management, a mixture of the genotypes JS-9560, JS-20-34, MAUS-47 and MACS-1460 was found most effective treatment. The plots with the genotypic mixtures of NRC-37, JS-9752, RSC-1046 and RKS-113 supported the least population of semiloopers. However, lowest population of leaf miner and girdle beetle was recorded in plots of JS-20-34 while the least population of stem fly was recorded in RSC-1046. The differences observed due to the genotypic combinations may be used for developing inset-pest management programmes in soybean.

Rotavirus A Infection Prevalence and Spatio-Temporal Genotype Shift among Under-Five Children in Amhara National Regional State, Ethiopia: A Multi-Center Cross-Sectional Study.

Background: Globally, rotavirus (RV) A (RVA) is the most common cause of severe and sometimes fatal diarrhea in young children. It is also the major cause of acute gastroenteritis among children in Ethiopia. Currently, the WHO has prequalified four RVA vaccines for universal childhood immunization. Ethiopia introduced the monovalent Rotarix vaccine into its national immunization program in 2013. Since then, only a few studies on the burden and genotype distribution of RVA infection post-vaccine introduction have been conducted (mostly at sentinel surveillance sites). Therefore, this study aimed to assess RVA prevalence and genotype distribution among children under five years in Ethiopia (February 2021-December 2022). Methods: This multi-center hospital-based cross-sectional study involved 537 diarrheic children under-five years old. Rotavirus A detection was conducted using a one-step reverse-transcriptase polymerase chain reaction (RT-PCR). Genotyping was conducted by Sanger sequencing of the VP7 (complete) and VP4 (partial) genes. Descriptive analysis and Pearson's chi-squared test were carried out using SPSS version 29. Phylogenetic analysis with 1000 bootstrap replicates was performed using MEGA version 11 software. Statistical significance was set at p < 0.05 for all analyses. Results: The prevalence of RVA infection among diarrheic children was 17.5%. The most prevalent G-types identified were G3 (37%), the previously uncommon G12 (28%), and G1 (20%). The predominant P-types were P[8] (51%), P[6] (29%), and P[4] (14%). The three major G/P combinations observed were G3P[8] (32.8%), G12P[6] (28.4%), and G1P[8] (19.4%). Phylogenetic analysis revealed clustering of Ethiopian strains with the globally reported strains. Many strains exhibited amino acid differences in the VP4 (VP8* domain) and VP7 proteins compared to vaccine strains, potentially affecting virus neutralization. Conclusions: Despite the high RVA vaccination rate, the prevalence of RVA infection remains significant among diarrheic children in Ethiopia. There is an observable shift in circulating RVA genotypes from G1 to G3, alongside the emergence of unusual G/P genotype combinations such as G9P[4]. Many of these circulating RVA strains have shown amino acid substitutions that may allow for neutralization escape. Therefore, further studies are warranted to comprehend the emergence of these unusual RVA strains and the diverse factors influencing the vaccine's diminished effectiveness in developing countries.

Association of Genetic Profile with Muscle Mass Gain and Muscle Injury Prevention in Professional Football Players after Creatine Supplementation.

In recent years, the study of creatine supplementation in professional athletes has been of great interest. However, the genetics involved in response to supplementation is unknown. The aim of this study was to analyse, for the first time, the relationship between muscle performance-related genes and the risk of an increased body mass index (BMI) and muscle mass and a decrease in fat mass in professional football players after creatine supplementation. For this longitudinal study, one hundred and sixty-one men's professional football players were recruited. The polymorphisms ACE I/D, ACTN3 c.1729C>T, AMPD1 c.34C>T, CKM c.*800A>G, and MLCK (c.49C>T and c.37885C>A) were genotyped using Single-Nucleotide Primer Extension (SNPE). To assess the combined impact of these six polymorphisms, a total genotype score (TGS) was calculated. The creatine supplementation protocol consisted of 20 g/day of creatine monohydrate for 5 days (loading dose) and 3-5 g/day for 7 weeks (maintenance dose). Anthropometric characteristics (body mass index (BMI), fat, and muscle mass) were recorded before and after the creatine supplementation protocol. Characteristics of non-contact muscle injuries during the 2022/2023 season were classified according to a consensus statement for injury recording. The results showed that the allelic frequencies of ACE and AMPD1 differed between responders and non-responders in muscle mass increase (all p < 0.05). Players with a TGS exceeding 54.16 a.u. had an odds ratio (OR) of 2.985 (95%CI: 1.560-5.711; p = 0.001) for muscle mass increase. By contrast, those with a TGS below 54.16 a.u. had an OR of 9.385 (95%CI: 4.535-19.425; p < 0.001) for suffering non-contact muscle injuries during the season. The increase in BMI and muscle mass in response to creatine supplementation in professional football players was influenced by a TGS derived from the combination of favourable genotypes linked to muscle performance. The CC genotype and C allele of AMPD1 were particularly associated with a higher likelihood of muscle mass increase under creatine supplementation in this group of professional football players.

Genetic Variants in p53 Pathway Genes Affect Survival of Patients with HBV-Related Hepatocellular Carcinoma.

P53 is a suppressor gene closely related to carcinogenesis. However, the associations between genetic variants in the p53 signaling pathway and prognosis in hepatitis B virus (HBV)-related hepatocellular carcinoma (HCC) remain unknown. The current study aims to analyze associations between the single nucleotide polymorphisms (SNPs) in p53 pathway-related genes and survival of patients with HBV-HCC. We evaluated the associations between 4698 SNPs in 70 genes of the p53 pathway and overall survival (OS) of 866 patients in additive genetic models by using Cox proportional hazards regression analysis. Stepwise multivariable Cox regression analysis was conducted to determine the independent effects of identified SNPs in single-locus analyses. The expression of quantitative trait loci (eQTL) was also analyzed using data from GTEx and 1000 Genomes Project, and functional prediction of SNPs was performed by using RegulomeDB v2.2, 3DSNP v2.0, HaploReg v4.2 and VannoPortal. We found that two novel SNPs of CD82 rs7925603 A > G and PMAIP1 rs4396625 A > T, were significantly and independently associated with OS [adjusted hazards ratios (HRs) and 95% confidence intervals (CI) were 1.27 (1.10-1.48) and 0.77 (0.66-0.91), respectively; P = 0.001 and = 0.002, respectively] and that the combined risk genotypes of these SNPs showed a significant association with OS in patients with HBV-HCC (P trend < 0.001). Further eQTL analysis in the GTEx dataset showed that the rs7925603 G allele was associated with lower CD82 mRNA expression levels, while the rs4396625 T allele was associated with higher PMAIP1 mRNA expression levels in whole blood cells. We identified two observed survival-associated SNPs in CD82 and PMAIP1 in the p53 pathway, which influenced HBV-HCC survival possibly through a mechanism of altering mRNA expression. Large studies are warranted to validate our findings.