Major Allele Research Articles

Association of Renalase rs2296545 gene polymorphism to susceptibility of hypertension in Iraqi patients

Hypertension is a major public health problem due to its high prevalence all around the globe. Renalase is involved in the regulation of blood pressure and cardiac function via degrading catecholamines in the blood circulation. This study aims to investigate the association of polymorphism of renalase gene rs(2296545) to the susceptibility of hypertension Iraqi hypertensive patients .The results of this study revealed that the proportion of hypertensive patients with GG genotype was markedly higher with significant difference compared to controls 40% vs.5%,p≤ 0.01, CC genotype revealed remarkable proportion among hypertensive patients.Genotype CC represented the highest percentage among patients and healthy subjects 46% vs.70, P> 0.05.The C allele was the major allele among hypertensive patients and controls. Susceptibility analysis of renalase gene ( rs2296545) gene polymorphism with hypertension showed that GG genotype was significant risk association among hypertensive patients in both females and males OR =12.6 ( CI 95%1.65-97.26) p≤ 0.01, while, rs2296545CG and CC are protective OR=0.41( CI95%0.11-1.50) OR=0.4 (CI95%0.13-1.17) ,P> 0.05 respectively. We conclude that The renalase rs2296545 GG genotype and G allele could be a risk factor for hypertensive patients .

HSPA8 Single-Nucleotide Polymorphism Is Associated with Serum HSC70 Concentration and Carotid Artery Atherosclerosis in Nonalcoholic Fatty Liver Disease.

There is an association between nonalcoholic fatty liver disease (NAFLD) and atherosclerosis, but the genetic risk of atherosclerosis in NAFLD remains unclear. Here, a single-nucleotide polymorphism (SNP) of the heat shock 70 kDa protein 8 (HSPA8) gene was analyzed in 123 NAFLD patients who had been diagnosed using a liver biopsy, and the NAFLD phenotype including the maximum intima–media thickness (Max-IMT) of the carotid artery was investigated. Patients with the minor allele (A/G or G/G) of rs2236659 showed a lower serum heat shock cognate 71 kDa protein concentration than those with the major A/A allele. Compared with the patients with the major allele, those with the minor allele showed a higher prevalence of hypertension and higher Max-IMT in men. No significant associations between the HSPA8 genotype and hepatic pathological findings were identified. In decision-tree analysis, age, sex, liver fibrosis, and HSPA8 genotype were individually associated with severe carotid artery atherosclerosis (Max-IMT ≥ 1.5 mm). Noncirrhotic men aged ≥ 65 years were most significantly affected by the minor allele of HSPA8. To predict the risk of atherosclerosis and cardiovascular disease, HSPA8 SNP genotyping might be useful, particularly for older male NAFLD patients.

TGF-β/VEGF-A Genetic Variants Interplay in Genetic Susceptibility to Non-Melanocytic Skin Cancer.

Differential genetically determined expression of transforming growth factor-β (TGF-β pathway and of vascular endothelial growth factor-A (VEGF-A) might modulate the molecular “milieu” involved in the etio-pathogenesis of non-melanoma skin cancer (NMSC). We have evaluated the frequency of some functionally relevant SNPs of TGF-β and VEGF-A genes in 70 NMSC patients and 161 healthy controls, typed for TGF-β1 rs1800471, TGF-β2 rs900, TGF-βR1 rs334348 and rs334349, TGF-βR2 rs4522809 and VEGF-A rs3025039 SNPs. TGF-βR2 rs1800629G allele and related genotypes were found to be associated with a possible protective role against NMSC, whereas VEGF-A rs3025039T was associated with an increased risk. To evaluate the effect of genotype combinations on NMSC susceptibility, we determined the frequencies of 31 pseudo-haplotypes due to non-random linkage among alleles of loci not lying on the same chromosome. Two pseudo-haplotypes that imply a minor allele of TGF-βR2 or minor allele of VEGF-A SNPs combined with major alleles of the other SNPs were, respectively, associated with a protective effect, and susceptibility to NMSC. In addition, a pseudo-haplotype involving minor alleles of TGF-β2 rs900, TGF-βR1 rs334348 and rs4522809 SNPs might be a susceptibility marker for NMSC. In conclusion, our data suggest that a complex interplay among the genetic polymorphisms of TGF-β, TGF-β receptors and VEGF-A genes might influence the net effect of genetic background of the patients on NMSC development. This might be relevant in the risk evaluation, diagnosis and treatment of NMSC.

Small Peptide Derivatives Within the Carbohydrate Recognition Domain of SP-A2 Modulate Asthma Outcomes in Mouse Models and Human Cells.

Surfactant Protein-A (SP-A) is an innate immune modulator that regulates a variety of pulmonary host defense functions. We have shown that SP-A is dysfunctional in asthma, which could be partly due to genetic heterogeneity. In mouse models and primary bronchial epithelial cells from asthmatic participants, we evaluated the functional significance of a particular single nucleotide polymorphism of SP-A2, which results in an amino acid substitution at position 223 from glutamine (Q) to lysine (K) within the carbohydrate recognition domain (CRD). We found that SP-A 223Q humanized mice had greater protection from inflammation and mucin production after IL-13 exposure as compared to SP-A-2 223K mice. Likewise, asthmatic participants with two copies the major 223Q allele demonstrated better lung function and asthma control as compared to asthmatic participants with two copies of the minor SP-A 223K allele. In primary bronchial epithelial cells from asthmatic participants, full-length recombinant SP-A 223Q was more effective at reducing IL-13-induced MUC5AC gene expression compared to SP-A 223K. Given this activity, we developed 10 and 20 amino acid peptides of SP-A2 spanning position 223Q. We show that the SP-A 223Q peptides reduce eosinophilic inflammation, mucin production and airways hyperresponsiveness in a house dust mite model of asthma, protect from lung function decline during an IL-13 challenge model in mice, and decrease IL-13-induced MUC5AC gene expression in primary airway epithelial cells from asthmatic participants. These results suggest that position 223 within the CRD of SP-A2 may modulate several outcomes relevant to asthma, and that short peptides of SP-A2 retain anti-inflammatory properties similar to that of the endogenous protein.

Study the Association of Nucleotide Polymorphisms in Platelet Receptor and Cytochrome P450 Genes with the Development of Resistance to Antiplatelet Drugs in Patients with Coronary Artery Disease

Aim. To study the association of nucleotide polymorphisms in platelet receptor and cytochrome P450 genes with the development of resistance to antiplatelet drugs in CHD patients.Material and Methods. The study included 243 patients diagnosed with CHD after coronary artery bypass surgery (CABG), including 140 patients in the acetylsalicylic acid (ASA) treatment group and 103 patients in the dual antiplatelet therapy (DAT) group. All patients were tested for platelet aggregation using an optical aggregometer with inducers: 5 mM ADP and 1 mM arachidonic acid (AA). DNA samples were analyzed by allele-specific PCR for the presence of polymorphisms rs2046934, rs1126643, rs5918, rs6065, rs4244285 in the platelet receptor and cytochrome P450 genes.Results. No statistically significant differences were found during comparison of the prevalence of the studied polymorphisms in the platelet receptor and cytochrome P450 genes between the groups of aspirin-sensitive and aspirin-resistant patients, as well as between the groups of clopidogrelsensitive and clopidogrel-resistant patients. No association between carriage of the minor and major alleles of the polymorphisms studied and the development of antiplatelet drug resistance was found. In the group of patients on ASA therapy, carriers of the C allele of the T1565C (rs5918) ITGB3 polymorphism had a higher rate of AA-induced platelet aggregation compared to carriers of the T allele (18,49±25,92 vs 10,43±17,34, р=0,004).Conclusion. Polymorphisms of P2RY12 (rs2046934), ITGA2 (rs1126643), ITGB3 (rs5918), GP1BA (rs6065), CYP2C19*2 (rs4244285) genes are not associated with antiplatelet drug resistance in both patients on ASC therapy and on DAT. The presence of minor alleles of the rs2046934, rs1126643, rs6065, rs4244285 polymorphisms are not associated with increased platelet aggregation activity before CABG.However, in the group of patients on ASA therapy C-allele carriers of the rs5918 polymorphism of the ITGB3 gene had a higher rate of AA-induced platelet aggregation compared to T-allele carriers.

Role of single nucleotide polymorphisms of the HSD3B1 gene (rs6203 and rs33937873) in the prediction of prostate cancer risk

3-β-hydroxysteroid dehydrogenase 1 (HSD3B1) is shown to affect dihydrotestosterone level in prostatic tissue which is a risk factor for prostate cancer (PC). The present study aimed to determine whether rs33937873 (G313A) and rs6203 (C338T) single nucleotide polymorphisms (SNP) in HSD3B1 gene was a potential risk factor for PC susceptibility and can predict the recurrence of PC in Egyptian patients. A total of 186 Egyptian patients were selected with incident primary PC and compared with 180 age healthy controls. The frequencies and the main effect of rs33937873 and rs6203 in HSD3B1 were compared and investigated between the patients and control using genotyping technique and statistical analysis. The mutant GA genotype of G313A in rs33937873 SNP was considered as an independent risk for PC in the multivariate regression analysis [odds ratio (OR)=2.7, 95% confidence intervals (CI): 1.2-5.5, P=0.01] together with positive history of hypertension (HTN) (OR=6.2, 95% CI: 3.2-12.1, P=0.0001) and begin prostatic hyperplasia (BPH; OR=8.9, 95% CI: 4.5-17.5, P=0.0001). Conversely, in rs6203 (C338T), C allele is considered as major risk allele in the development of PC (OR=1.8, 95% CI: 1.3-2.4, P=0.0003). The univariate logistic regression analyses indicated that CC genotype of rs6203 was a PC risk factor (OR=1.9, 95% CI: 1.3-2.9, P=0.002). In addition, the frequency of the A-C haplotype established by rs33937873-rs6203 was also significantly higher for PC (P=0.013). The predication of PC recurrence was associated only with positive family history (OR=7.7, 95% CI: 2.3-25.9, P=0.001) and not for The G313A and C338T SNPs. These results suggested that the two HSD3B1 polymorphisms rs33937873 and rs6203 may modify the risk of PC, particularly among patients with HTN and history of BPH, suggesting them as prominent future markers for prediction of PC risk.

Histopathology of Psoriatic Arthritis Synovium-A Narrative Review.

Psoriatic arthritis (PsA) is a phenotypically heterogeneous chronic inflammatory disease associated to type I major histocompatibility complex alleles whose complex pathogenesis is still not completely understood. The psoriatic synovium shares general features of chronic inflammation with rheumatoid arthritis (RA) and other arthritis, such as hyperplasia of the intimal lining layer, sublining influx of inflammatory cells and neoangiogenesis, but recognizing disease-specific histopathologic findings may help in diagnosis and definition of therapeutic targets. Available literature reports conflicting data regarding the extension of lining hyperplasia, that does not allow depiction from RA. Sublining inflammatory cells consist of T and B cells and macrophages, plasma cells, mast cells and follicular dendritic cells, with a higher amount of overall T, mast cell and IL-17 producing CD8+ T lymphocytes and lower proportion of plasma cells when compared to the rheumatoid synovium. The amount of synovium IL17+ CD8+ T cells correlates positively to measures of disease activity. Lymphoid follicles with characteristics of germinal centers have been identified, similar to the ones described in RA. Neoangiogenesis is more prominent in PsA but can also be an outstanding feature in some RA samples, and different molecules involved in the process appear to have different influence in each disease. IL-17 and IL-22 expression in the synovium does not allow depiction between diseases. Among other cytokines and molecules likely implicated in disease physiopathology, only IL-35 is demonstrated to be reduced in PsA when compared to RA.

РОЛЬ ПОЛИМОРФИЗМОВ ГЕНОВ NOS3 И CYBA В ФОРМИРОВАНИИ ОСЛОЖНЕНИЙ ХРОНИЧЕСКОГО ВИРУСНОГО ГЕПАТИТА В Название объекта Название объекта в переводе ФИО автора / список авторов Место работы автора ORCID Ключевые слова Аннотация

In the Republic of Sakha (Yakutia), persistently high incidence rates of CVH remain, as well as mortality rates from complications of liver cirrhosis (LC), as the most common complication. It seems relevant to search for genetic predictors of early development of severe complications in CVH patients in the Yakut population. They can be polymorphic variants of the genes for endothelial dysfunction and oxidative stress NOS3 and CYBA. The collection of representative material was carried out on the basis of the Infectious Diseases Department of the State Budgetary Institution of the Republic of Sakha (Yakutia) of the Yakut Republican Clinical Hospital. In total, 47 DNA samples of patients with chronic viral hepatitis В and liver cirrhosis in its outcome, hospitalized in the Infectious Diseases Department from September 2020 to June 2021, were studied. The control group consisted of patients not infected with viral hepatitis, as well as without pathology of the hemostasis system. The experimental part of the study was carried out by real-time PCR with the melting of hybridization products with a fluorescent label, followed by analysis of the RealBest-Genetics melting curves. As a result of the PCR-RFLP analysis of the rs1799983 polymorphism of the NOS3 gene among patients with chronic viral hepatitis, the T allele frequency was 0.09, and the G allele frequency was 0.91. The frequency of the C allele of the rs2070744 polymorphism of the NOS3 gene was 0.05, the frequency of the T allele was 0.95. The frequency of occurrence of the major allele C of the rs4673 polymorphism of the CYBA gene was 0.78, the minor allele T was 0.22. The relationship between the carriage of polymorphisms of these genes and the disease was not found. However, it was found that carriers of the mutant allele for the rs1799983 polymorphism of the NOS3 gene were 1.81 times more likely to develop liver cirrhosis (95 % CI, odds in the groups 0.176–0.098), carriers of the mutant allele for the rs4673 polymorphism of the CYBA gene were more likely to develop cirrhosis liver cirrhosis is 1.9 times higher (95 % CI, odds in groups 0.211–0.111), in carriers of the mutant allele for the rs2070744 polymorphism of the NOS3 gene, the probability of developing liver cirrhosis is 2.03 times higher (95 % CI, odds in groups 0.181–0.089 ). In carriers of the mutant allele for the rs4673 polymorphism of the CYBA gene, shortening of PT and APTT (17.79 ± 10.26 and 35.13 ± 7.82 sec) is observed, which may indicate a greater tendency of this group to hypercoagulability. In carriers of the mutant allele for the rs2070744 polymorphism of the NOS3 gene, shortening of PT and APTT (11.56 ± 0.99 and 30.12 ± 4.45 sec) is observed, which may also indicate a greater tendency of this group to hypercoagulability.

Phylogenetic analysis of Colchicum (Colchicaceae) genus by molecular markers from nuclear and chloroplast genome

We evaluated the patterns of genetic variation of 16 Colchicum species, including 37 different genotypes, using RAPD marker and trnL–trnF chloroplast DNA sequence. A total of 861 polymorphic alleles through RAPDs showed a mean of 33.88 ± 3.80 alleles per primer, while mean major allele frequency was 0.067 ± 0.05. The sequence length of trnL–trnF ranged from 1022 bp to 1081 bp. The phylogenetic tree was constructed to understand the relationship between Colchicum species and the discrimination power of the nuclear and chloroplast genome for species. The results showed that trnL–trnF gene region grouped Colchicum species well in comparison with RAPD analysis. This data was also supported by haplotype network analysis, structure analysis and PCA (Principle Component Analysis). This study showed that there is a need for a characterization that contains more molecular and morphological methods to correctly distinguish Colchicum species.

Influence of NOS1AP Risk Variants on the Corrected QT (QTc) Interval in the Pharmacotherapy of Schizophrenia.

The variants of the gene for nitric oxide synthase 1 adaptor protein (NOS1AP) are associated with schizophrenia and cardiovascular deficits involving corrected QT (QTc) interval prolongation. Here, we investigated a possible pharmacogenetic effect of antipsychotic treatment on QTc length in interaction with two NOS1AP variants (rs12143842 and rs10494366) whose minor alleles are associated with increased QTc interval length. We conducted a retrospective analysis of electrocardiographic (ECG) and genotype data of 239 patients diagnosed with schizophrenia. We converted antipsychotics dosage to chlorpromazine equivalents and defined daily doses. We analysed the effects of the minor (i. e. rs12143842-CT/TT and rs10494366-GT/GG) and major (i. e. rs12143842-CC and rs10494366-TT) allele genotypes to QTc interval for female and male participants separately. As expected, rs12143842 and rs10494366 exhibit strong linkage disequilibrium. Both polymorphisms had no direct effect on antipsychotic use or QTc interval. However, there was a continuous increase in QTc interval with increasing antipsychotic dosage in males. For both variants, positive correlation of QTc length with antipsychotic dosage was found in homozygous male carriers of the major alleles (i. e. rs12143842-CC and rs10494366-TT), but not in minor allele carriers. There was no significant interaction between antipsychotic dosage and QTc interval for either genotype in female patients. In this study, a significant interaction was found between both NOS1AP variants, rs12143842 and rs10494366, and antipsychotic treatment on the QTc interval in a sex-dependent manner. Our findings might be relevant for adequate antipsychotic treatment in rs12143842 and rs10494366 major allele carriers.

Introgression of gluten protein genes associated with the D-genome of bread wheat into durum wheat

In the past thirty years many attempts have been addressed to the possibility to improve the breadmaking characteristics of durum wheat. Since the low breadmaking quality of durum wheat was mainly attributed to the absence of suitable high (HMW-GS) – and low (LMW-GS) molecular weight glutenin subunits, different approaches have been used to introgress D-genome associated LMW-GS HMW-GS, present at the linked Gli-D1/Glu-D3 and Glu-D1 loci. In this paper two sets of durum wheat lines with different introgressions of the D-related glutenin proteins transferred on the short and long arm of chromosome 1A of the recipient variety Svevo, have been characterised. The first set included two lines possessing either the Chinese Spring- (CS) or the Cheyenne- (CNN) type of major alleles at the Gli-D1/Glu-D3 loci, transferred on the short arm of Svevo chromosome 1A. The second group included four lines obtained from crosses between the two lines with the CNN- or CS-type of 1DS alleles with previously obtained durum wheat lines carrying translocations involving the HMW-GS loci Glu-D1a (2 + 12) or Glu-D1d (5 + 10). Quality traits and rheological data were determined for the six translocation lines grown in two different years and compared with the durum variety Svevo. The two translocation lines carrying the two different variants (CS- or CNN-type) at the Gli-D1/Glu-D3 loci behaved differently, the former showing increase of quality characteristics and rheological parameter compared to Svevo, the latter being substantially similar to Svevo. On the contrary, all four double recombinant lines showed maximum values of gluten index and major effects on alveographic parameters due to the presence of the Glu-D1 HMW-GS.

Identification of a novel frameshift variant in the KMT2A gene of a child with Wiedemann-Steiner syndrome

To analyze pathogenic variant s of KMT2A gene in a child with Wiedemann-Steiner syndrome (WDSTS) and provide reliable evidences for clinical diagnosis of WDSTS. Whole-DNAs were extracted from an 9 years-old boy and his parents. Trio-whole exome sequencing (trio-WES) was performed to identify candidate pathogenic variants that can explain the boy's condition and sanger sequencing was conducted to prove it. The impact of detected variants were predicted and validated by bioinformatics tools. A de novo frameshift variant c.10488dupG (p.Leu3498Thrfs*41) in exon 27 of KMT2A gene was detected and this de novo variant (PS2) had not been reported in the world previously. This frameshift variant was absent in major allele frequency databases (PM2) and had been predicted to be pathogenic based on MutationTaster. Through HomoloGene and CD-search system, the 3498 locus (Leu) in KMT2A protein, which was an important histone modifying enzyme that regulated gene expression in early embryonic development and encoded by the KMT2A gene, was predicted as a high conserved locus (PP3), and that replacement of Lue3498 may result in frame-shifts with premature termination in 3539 locus by introducing stop codon, causing deletion of multiple functional domains which all played important roles on histone modifications and recognition (PVS1+PM1). According to the American College of Medical Genetics and Genomics variant classification guideline, the variant c.10488dupG (p.Leu3498Thrfs*41) in KMT2A was classified as pathogenic variant (PVS1+PS2+PM1+PM2+PP3). The patient's condition may be attributed to the de novo frameshift variant c.10488dupG (p.Leu3498Thrfs*41) in KMT2A gene. This study reported a pathogenic KMT2A variant that had not been reported previously in WDSTS, it expanded the genotypic spectrums of KMT2A variants.

The glucocorticoid receptor represses, whereas C/EBPβ can enhance or repress CYP26A1 transcription

SummaryRetinoic acid (RA) counters insulin’s metabolic actions. Insulin reduces liver RA biosynthesis by exporting FoxO1 from nuclei. RA induces its catabolism, catalyzed by CYP26A1. A CYP26A1 contribution to RA homeostasis with changes in energy status had not been investigated. We found that glucagon, cortisol, and dexamethasone decrease RA-induced CYP26A1 transcription, thereby reducing RA oxidation during fasting. Interaction between the glucocorticoid receptor and the RAR/RXR coactivation complex suppresses CYP26A1 expression, increasing RA’s elimination half-life. Interaction between CCAAT-enhancer-binding protein beta (C/EBPβ) and the major allele of SNP rs2068888 enhances CYP26A1 expression; the minor allele restricts the C/EBPβ effect on CYP26A1. The major and minor alleles associate with impaired human health or reduction in blood triglycerides, respectively. Thus, regulating CYP26A1 transcription contributes to adapting RA to coordinate energy availability with metabolism. These results enhance insight into CYP26A1 effects on RA during changes in energy status and glucocorticoid receptor modification of RAR-regulated gene expression.

Prediction of various blood group systems using Korean whole-genome sequencing data.

AimsThis study established blood group analysis methods using whole-genome sequencing (WGS) data and conducted blood group analyses to determine the domestic allele frequency using public data from the Korean whole sequence analysis of the Korean Reference Genome Project conducted by the Korea Disease Control and Prevention Agency (KDCA).Materials and methodsWe analyzed the differences between the human reference sequences (hg19) and the conventional reference cDNA sequences of blood group genes using the Clustal Omega website, and established blood group analysis methods using WGS data for 41 genes, including 39 blood group genes involved in 36 blood group antigens, as well as the GATA1 and KLF1 genes, which are erythrocyte-specific transcription factor genes. Using CLC genomics Workbench 11.0 (Qiagen, Aarhus, Denmark), variant analysis was performed on these 41 genes in 250 Korean WGS data sets, and each blood group’s genotype was predicted. The frequencies for major alleles were also investigated and compared with data from the Korean rare blood program (KRBP) and the Erythrogene database (East Asian and all races).ResultsAmong the 41 blood group-related genes, hg19 showed variants in the following genes compared to the conventional reference cDNA: GYPA, RHD, RHCE, FUT3, ACKR1, SLC14A1, ART4, CR1, and GCNT2. Among 250 WGS data sets from the Korean Reference Genome Project, 70.6 variants were analyzed in 205 samples; 45 data samples were excluded due to having no variants. In particular, the FUT3, GNCT2, B3GALNT1, CR1, and ACHE genes contained numerous variants, with averages of 21.1, 13.9, 13.4, 9.6, and 7.0, respectively. Except for some blood groups, such as ABO and Lewis, for which it was difficult to predict the alleles using only WGS data, most alleles were successfully predicted in most blood groups. A comparison of allele frequencies showed no significant differences compared to the KRBP data, but there were differences compared to the Erythrogene data for the Lutheran, Kell, Duffy, Yt, Scianna, Landsteiner-Wiener, and Cromer blood group systems. Numerous minor blood group systems that were not available in the KRBP data were also included in this study.ConclusionsWe successfully established and performed blood group analysis using Korean public WGS data. It is expected that blood group analysis using WGS data will be performed more frequently in the future and will contribute to domestic data on blood group allele frequency and eventually the supply of safe blood products.

Sex-different interrelationships of rs945270, cerebral gray matter volumes, and attention deficit hyperactivity disorder: a region-wide study across brain

Previous genome-wide association studies (GWAS) reported that the allele C of rs945270 of the kinectin 1 gene (KTN1) most significantly increased the gray matter volume (GMV) of the putamen and modestly regulated the risk for attention deficit hyperactivity disorder (ADHD). On the other hand, ADHD is known to be associated with a reduction in subcortical and cortical GMVs. Here, we examined the interrelationships of the GMVs, rs945270 alleles, and ADHD symptom scores in the same cohort of children. With data of rs945270 genotypes, GMVs of 118 brain regions, and ADHD symptom scores of 3372 boys and 3129 girls of the Adolescent Brain Cognition Development project, we employed linear regression analyses to examine the pairwise correlations adjusted for the third of the three traits and other relevant covariates, and examine their mediation effects. We found that the major allele C of rs945270 modestly increased risk for ADHD in males only when controlling for the confounding effects of the GMV of any one of the 118 cerebral regions (0.026 ≤ p ≤ 0.059: Top two: left and right putamen). This allele also significantly increased putamen GMV in males alone (left p = 2.8 × 10−5, and right p = 9.4 × 10−5; α = 2.1 × 10−4) and modestly increased other subcortical and cortical GMVs in both sexes (α < p < 0.05), whether or not adjusted for ADHD symptom scores. Both subcortical and cortical GMVs were significantly or suggestively reduced in ADHD when adjusted for rs945270 alleles, each more significantly in females (3.6 × 10−7 ≤ p < α; Top two: left pallidum and putamen) and males (3.5 × 10−6 ≤ p < α), respectively. Finally, the left and right putamen GMVs reduced 14.0% and 11.7% of the risk effects of allele C on ADHD, and allele C strengthened 4.5% (left) and 12.2% (right) of the protective effects of putamen GMVs on ADHD risk, respectively. We concluded that the rs945270-GMVs-ADHD relationships were sex-different. In males, the major allele C of rs945270 increased risk for ADHD, which was compromised by putamen GMVs; this allele also but only significantly increased putamen GMVs that then significantly protected against ADHD risk. In females, the top two GMVs significantly decreasing ADHD risk were left pallidum and putamen GMVs. Basal ganglia the left putamen in particular play the most critical role in the pathogenesis of ADHD.

Анализ факторов риска формирования дефицита здоровья и его индикаторных показателей у детей с врожденными пороками сердца через два года после радикальной операции

Our research goal was to analyze risk factors that could cause health disorders in children two years after a radical heart surgery. It is vital for optimizing diagnostics and predicting negative outcomes of surgical treatment for congenital heart diseases (CHD) using data taken from anamnesis vitae and genetic indicators. We performed prospective cohort monitoring of 89 children with CHD during two years starting from the moment they had a radical heart surgery. The study design included the following stages: quality of life assessment using “Cardiac Module” in the Pediatric Quality of Life Questionnaire (USA, 2001); collecting data to create anamnesis vitae by questioning; identifying types of polymorphisms of xenobiotic biotransformation genes, inborn and adaptive immunity genes participating in embryogenesis of the cardiovascular system; logistic regression incremental multifactorial analysis of independent variables in anamnesis vitae, peculiarities of a radical surgery, health indicators prior to an operation, as well as polymorph variants of the examined genes with dependent variants: types of functioning and the complex integral health indicator two years after surgical treatment. The complex integral health indicator and indicators of physical functioning were significant ones in 2-year dynamics of patients’ health after surgical treatment for CHD. These indicators reflected children’s quality of life long time after a radical heart surgery. Health deficiency and impaired quality of life two years after a radical heart surgery was associated with HLADRB104, HLADRB111, HLADRB112, HLADRB113 alleles and the major allele Т in the polymorph variant of CYP1A1 T/C (rs1048943) gene. Influence exerted by these alleles on quality of life long time after a radical heart surgery is determined by long-term toxic inflammation in an operated heart. CHD severity, an age when a radical surgery was performed, as well as unsatisfactory material benefits and living conditions are common medical and social risk factors that cause health deficiency and impaired quality of life long time after a radical heart surgery.

Analysis of risk factors causing health deficiency and its indicators in children with congenital heart diseases two years after radical surgery

Our research goal was to analyze risk factors that could cause health disorders in children two years after a radical heart surgery. It is vital for optimizing diagnostics and predicting negative outcomes of surgical treatment for congenital heart diseases (CHD) using data taken from anamnesis vitae and genetic indicators. We performed prospective cohort monitoring of 89 children with CHD during two years starting from the moment they had a radical heart surgery. The study design included the following stages: quality of life assessment using “Cardiac Module” in the Pediatric Quality of Life Questionnaire (USA, 2001); collecting data to create anamnesis vitae by questioning; identifying types of polymorphisms of xenobiotic biotransformation genes, inborn and adaptive immunity genes participating in embryogenesis of the cardiovascular system; logistic regression incremental multifactorial analysis of independent variables in anamnesis vitae, peculiarities of a radical surgery, health indicators prior to an operation, as well as polymorph variants of the examined genes with dependent variants: types of functioning and the complex integral health indicator two years after surgical treatment. The complex integral health indicator and indicators of physical functioning were significant ones in 2-year dynamics of patients’ health after surgical treatment for CHD. These indicators reflected children’s quality of life long time after a radical heart surgery. Health deficiency and impaired quality of life two years after a radical heart surgery was associated with HLADRB104, HLADRB111, HLADRB112, HLADRB113 alleles and the major allele Т in the polymorph variant of CYP1A1 T/C (rs1048943) gene. Influence exerted by these alleles on quality of life long time after a radical heart surgery is determined by long-term toxic inflammation in an operated heart. CHD severity, an age when a radical surgery was performed, as well as unsatisfactory material benefits and living conditions are common medical and social risk factors that cause health deficiency and impaired quality of life long time after a radical heart surgery.

APO E GENE POLYMORPHISM (C112R, R158C) AND LIPID PROFILE IN HYPERTENSIVE PATIENTS

Objective: Apo E is one of the major proteins in plasma lipoproteins rich in triglycerides. It presents a genetic polymorphism controlled by three dominant co-alleles coding for isoforms (Apo E2, Apo E3 and Apo E4). The aim of this study is to determine the polymorphism of Apo E gene (C112R, R158C) in hypertensive patients, and correlate it with the lipid profile. Design and method: This study included 105 hypertensive patients, mean of age (59.60 ± 10.73) years, 69 women (65.71%) and 36 men (34.29%), with complete data on anthropometric indices, fasting lipids: total cholesterol (CT), triglycerides (TG), HDLc and LDLc, smoking status, physical activities and Apo E genotype polymorphism by real time PCR. Results: In our series, dyslipidemia was found in 42% of patients, the most prominent lipid abnormalities are elevation of total cholesterol (49.46%), hypertriglyceridemia (39.78%) and hypoHDLemia (60%). The genotypic frequencies were respectively: E3/E3 (75.6%) which is the major allele, followed by E3/E4 (12.55%), E2/E3 (7.20%), E4/E4 (2.30%) and E2/E4 (2.35%). The genotype E4/E4 were not found in our series. The mean serum concentrations of the atherogenic lipids (CT) were significantly increased in heterozygous polymorphism with E2/E3 allele (p = 0.015) and E2/E4 allele (p = 0.017), for LDLc with E2/E3 allele (p = 0.014) and E2/E4 (p = 0.03). Conclusions: The preliminary results of our study suggest that Apo E genotyping have an impact on serum lipid parameters. Further studies of interactions between genes and environmental factors will contribute to the understanding of differences of coronary risk amongst ethnic groups.

Genetic diversity and marker trait association for phytophthora resistance in chilli.

Chilli is an important commercial crop with positive returns tendency. Phytophthora root rot causes drastic damage to chilli plant. Dearth of detecting marker trait associations is a major hinderance in practicing marker assisted selection in chilli breeding. Herein, 110 chilli accessions were assessed for 15 agronomic traits under control and disease infected conditions for two crop seasons (2018-2019). The SSR genotyping revealed high values of major allele frequency (MAF = 0.70), genetic diversity (GD = 0.39) and Polymorphic Information Content (PIC = 0.31). Principal coordinate analysis and population structure analysis showed distribution of diverse genotypes in all groups by dividing 110 genotypes in three populations and nine sub-populations. The UPGMA based Archaeopteryx tree was in concordance with population structure analysis. Linkage disequilibrium analysis evaluated that LD decays within 3-10bp. Marker trait association (MTA) revealed the associations of 35 SSRs with 14 morphological traits. The significant MTA for marker CAeMS073 with relative leaf damage (RLD, 0.183 R2) under control and treated conditions was consistently observed in both models. The markers, CAMS173 and CAMS194 were found to be strongly associated with RLD and Disease Index (DI), respectively. The absence of MTA was detected for height of first branch. The MTAs reported in this study can facilitate marker assisted breeding for developing chilli germplasm resistant against Phytophthora capsici.

Association of matrix metalloproteinase-8 gene promoter polymorphisms with type II diabetes mellitus in Syrian population

ObjectivesMatrix metalloproteinase (MMP)-8 is an enzyme that cleaves extracellular matrix (ECM). It is involved in many diseases' pathology including diabetes mellitus type II (DM). In MMP-8 gene promoter region, there are many polymorphisms with an important role in gene transcription modifying and protein production. -381A/G and -799 C/T SNPs are the most effective polymorphisms, and our study is the first work aimed to evaluate the association between these polymorphisms and DM susceptibility in Syrian population. Designstudy sample included 140 subjects allocated into two groups: H= healthy control, DM= diabetes mellitus. MMP-8 SNPs were determined by restriction fragment length polymorphism-polymerase chain reaction (RFLP-PCR) technique. ResultsThe frequencies of genotypes were significantly different between study groups (adjusted OR =3.621, 95% CI: 1.391-9.428, P = 0.008 for -381GG genotype), and (OR =4.941, 95% CI: 1.640-14.890, P = 0.005 for -799TT genotype). Subjects with minor alleles seem to be more likely to develop DM more than those with the major alleles (OR=2.842, P = 0.01 for G) and (OR =3.995, P = 0.001 for T). ConclusionThis study data has illustrated that there could be a remarkable association between MMP-8 gene promoter polymorphisms -381A/G and -799C/T and diabetic susceptibility in Syrian population.