Polymorphic variants of the genes for enzymes of the antioxidant system, apoptosis and inflammation as potential predictors of myocardial infarction.

Myocardial infarction (MI) is a multifactorial polygenic disease that develops as a result of a complex interaction of numerous genetic factors and the external environment. Accordingly, the contribution of each of them separately is usually not large and may significantly depend on the state of other accompanying factors. The purpose of the study was to search for informative predictors of MI risk based on polygenic analysis of polymorphic variants of (1) the antioxidant defense enzyme genes PON1 (rs662), PON2 (rs7493), CAT (rs1001179), MSRA (rs10098474) and GSTP1 (rs1695); (2) the apoptosis genes CASP8 (rs3834129), TP53 (rs1042522) and BCL2 (rs12454712); and (3) the inflammation genes CRP (rs1205), CX3CR1 (rs3732378), IL6 (rs1800795) and CCL2 (rs1024611).

Polygenic markers of survival and longevity in the antioxidant genes PON1, PON2, MTHFR, MSRA, SOD1, NQO1, and CAT in a 20-year follow-up study in the population from the Volga-Ural region.

Background: Genetic background of healthy or pathological styles of aging and human lifespan is determined by joint gene interactions. Lucky combinations of antioxidant gene polymorphisms can result in a highly adaptive phenotype, providing a successful way to interact with external triggers. Our purpose was to identify the polygenic markers of survival and longevity in the antioxidant genes among elderly people with physiological and pathological aging.

Role of PI3K/AKT/mTOR signaling pathway and sirtuin genes in chronic obstructive pulmonary disease development.

Chronic obstructive pulmonary disease (COPD) is a multifactorial disease of the respiratory system which develops as a result of a complex interaction of genetic and environmental factors closely related to lifestyle. We aimed to assess the combined effect of the PI3K/AKT/mTOR signaling pathway (PIK3R1, AKT1, MTOR, PTEN) and sirtuin (SIRT1, SIRT3, SIRT6) genes to COPD risk. SNPs of SIRT1 (rs3758391, rs3818292), SIRT3 (rs3782116, rs536715), SIRT6 (rs107251), AKT1 (rs2494732), PIK3R1 (rs10515070, rs831125, rs3730089), MTOR (rs2295080, rs2536), PTEN (rs701848, rs2735343) genes were genotyped by real-time polymerase chain reaction (PCR) among 1245 case and control samples.

[Multiple sclerosis in the Republic of Bashkortostan: population-specific genetic predictors and the results of a 20-year clinical follow-up study].

Objective: Identification of a complex of genetic predictors of multiple sclerosis (MS) based on previously obtained results in genome-wide association studies of disease markers (GWAS markers) in a population of MS patients and healthy individuals of the Republic of Bashkortostan (Russian Federation) using polygenic detection.

Material And Methods: The total study group consisted of 2048 people (641 patients with MS and 1407 healthy individuals) who permanently resided in the Republic of Bashkortostan and belonged to the Bashkir (325), Russian (772) or Tatar (951) nationalities. The analysis of association between MS and polymorphisms previously associated with the disease according to GWAS data was performed.

Alu Deletions in and Genes Are Key Components of Polygenic Predictors of Longevity.

Longevity is a unique human phenomenon and a highly stable trait, characterized by polygenicity. The longevity phenotype occurs due to the ability to successfully withstand the age-related genomic instability triggered by Alu elements. The purpose of our cross-sectional study was to evaluate the combined contribution of , , *, , , , , , and Alu elements to longevity.

Multilocus evaluation of genetic predictors of multiple sclerosis.

Background: Genome-wide association studies identified numerous susceptibility loci for multiple sclerosis in populations of European ancestry, but the associations are not always reproducible in other populations due to admixture and different linkage disequilibrium patterns obscuring true association signals.

Objective: Our aim was to identify genetic predictors of multiple sclerosis in three ethnically homogenous populations from the Volga-Ural region of Russian Federation.

Methods: In the largest to date study of multiple sclerosis in Russian population, involving 2048 participants from the Republic of Bashkortostan, Russian Federation (641 patients with multiple sclerosis and 1407 unaffected individuals), we performed replication analysis of previously identified genome-wide signals for multiple sclerosis.

[Complex association analysis of antioxidant genes polymorphic DNA-markers with age in the ethnic group of Abkhazians.].

For the first time in the ethnic group of Abkhazians, the association analysis of polymorphic DNA-markers of the antioxidant genes CAT (rs1001179), MSRA (rs10098474), GPX1 (rs1050450), GSR (rs1002149), GSTP1 (rs1695), SOD1 (rs2070424), SOD2 (rs4880), PON1 (rs662), PON2 (rs7493) with age was performed. Using ROC-analysis and logistic regression, it was found that the spectrum of alleles and genotypes frequencies of PON1 and GSTP1 genes polymorphic markers change throughout the studied age period (21-107 years old); the distribution of allele and genotype frequencies of CAT and SOD2 genes polymorphic markers changes within the age of 60 years. Multilocus genetic markers of longevity were determined by the Monte Carlo Markov chain method.

Genetic predictors of sick sinus syndrome.

Sick sinus syndrome (SSS) encompasses a group of conduction disorders characterized by the inability of sinoatrial node to perform its pacemaker function. Our aim was to identify genetic predictors of SSS in a prospective cohort of patients admitted to the clinic for pacemaker implantation using single-locus and multilocus approaches. We performed genotyping for polymorphic markers of CLCNKA (rs10927887), SCN10A (rs6795970), FNDC3B (rs9647379), MIR146A (rs2910164), SYT10 (rs7980799), MYH6 (rs365990), and KCNE1 (rs1805127) genes in the group of 284 patients with SSS and 243 healthy individuals.

The Relationship Between Chemokine and Chemokine Receptor Genes Polymorphisms and Chronic Obstructive Pulmonary Disease Susceptibility in Tatar Population from Russia: A Case Control Study.

Chronic obstructive pulmonary disease (COPD) is a chronic inflammatory lung disease affecting primarily distal respiratory pathways and lung parenchyma. This study aimed to determine possible genetic association of chemokine and chemokine receptor genes polymorphisms with COPD in a Tatar population from Russia. SNPs of CCL20, CCR6, CXCL8, CXCR1, CXCR2, CCL8, CCL23, CCR2, and CX3CL1 genes and their gene-gene interactions were analyzed for association with COPD in cohort of 601 patients and 617 controls.

[The analysis of association between multiple sclerosis and genetic markers identified in genome-wide association studies].

Objective: Our aim was to analyse the association with multiple sclerosis of the genetic markers of autoimmune disorders identified in genome-wide association studies in ethnically homogenous groups of Russians and Tatars residing in the Republic of Bashkortostan.

Material And Methods: We performed genotyping of the genetic variants rs2069762 in gene, rs759648 in gene, rs1800682 in gene and rs12708716 in gene in the study group consisting of 1724 people (547 patients with multiple sclerosis, 1177 representatives of the control group). We analysed the association of the studied genetic markers with multiple sclerosis using logistic regression under additive genetic model implemented in PLINK program with sex a covariate.

[The combined effect of genetic factors and attention deficit hyperactivity disorder on the development of dependence on synthetic cannabinoids].

Aim: To develop a model of assessment of individual risk of dependence on synthetic cannabinoids based on genetic factors and diagnosis of attention deficit hyperactivity disorder (ADHD).

Material And Methods: The study included 146 male adolescents using synthetic cannabinoids and 136 healthy people. The genetic study considered the combination of dependence on synthetic cannabinoids and ADHD.

Multilocus associations of inflammatory genes with the risk of type 1 diabetes.

Background: Genome-wide association studies have captured a large proportion of genetic variation related to type 1 diabetes mellitus (T1D). However, most of these studies are performed in populations of European ancestry and therefore the disease risk estimations can be inaccurate when extrapolated to other world populations.

Methods: We conducted a case-control study in 1866 individuals from the three major populations of the Republic of Bashkortostan (Russians, Tatars, and Bashkirs) in Russian Federation, using single-locus and multilocus approach to identify genetic predictors of T1D.

CXCL13 polymorphism is associated with essential hypertension in Tatars from Russia.

Essential arterial hypertension is a disease with distinct yet unexplored inflammatory component. Our aim was to assess the role of chemokine genes and their interaction in its development. Genotyping of polymorphic markers in six chemokine genes (CXCL13, CCL8, CCL16, CCL17, CCL18, and CCL23) was performed in the group of 522 men of Tatar ethnic origin from the Republic of Bashkortostan, Russia (213 patients with essential hypertension and 309 healthy individuals without history of cardiovascular disease).

Genetic determinants of essential hypertension in the population of Tatars from Russia.

Objective: Systemic inflammation and impaired function of endothelium play an important role in the development of hypertension. Our study aimed to analyze an association between essential hypertension and polymorphic markers in candidate genes in the group of 530 Tatars from the Republic of Bashkortostan, Russia.

Methods: The study group consisted of 216 male patients with essential hypertension (mean age 48.

[Combined Effect of Genetic Factors, Age, and Smoking on the Risk of Developing Myocardial Infarction].

Objective: to elaborate a complex model for myocardial infarction (MI) risk assessment considering the combined effect of genetic predisposition, age and smoking.

Materials And Methods: The study included two independent samples of ethnic Russians: 325 patients with MI and 185 individuals without history of cardiovascular diseases (controls) from the Moscow region, and 220 patients and 197 controls from the Republic of Bashkortostan. Genotyping of polymorphic loci of genes CRP (rs1130864), IFNG (rs2430561), TGFB1 (rs1982073), FGB (rs1800788) and PTGS1 (rs3842787) was performed.

[Alu insertion-deletion polymorphism of COL13A1 and LAMA2 genes: The analysis of association with longevity].

The distribution of allele and genotype frequencies of Alu(I/D) polymorphic sites in the COL13A1 and LAMA2 genes coding extracellular matrix protein subunits was characterized in an ethnically homogeneous group (Tatars from the Republic of Bashkortostan, Russia). It was established that the frequency of individuals with the COL13A1*D/*D genotype was higher in the senile age period. The LAMA2*I/*D genotype was predisposing to longevity among women.

[Analysis of FOXO1A and FOXO3A Gene Allele Association with Human Longevity].

Seeking human longevity association with gene polymorphisms in transcription factors in the Tatar ethnic group, we conducted an analysis for age-related genotype, frequencies in polymorphic sites of FOXO1A (rs4943794, 72327C>G) and FOXO3A (rs3800231, 35-2764A>G) genes. Genotyping was conducted by using the PCR-RFLP approach. According to the results of logistic regression analysis, during maturity and old age periods, a decrease in the number of FOXO1A*G/*G (OR = 0.

[Association of polymorphic markers of chemokine genes, their receptors, and CD14 gene with coronary atherosclerosis].

Atherosclerosis represents an inflammatory response to the disturbance of the endothelial layer in the arterial bloodstream. In the present study, an analysis of associations of polymorphic markers for the genes controlling synthesis of proteins involved in atherosclerosis pathogenesis in coronary atherosclerosis (CA) patients (217 subjects) and in a control group (250 subjects) was conducted. The following genes were examined: rs991804 (CCL2 gene), rs1126579 (CXCR2 gene), rs4074 (CXCL1 gene), rs4073 (CXCL8 gene), rs333 (CCR5 gene), rs2471859 (CXCR4 gene), rs1801157 (CXCL12 gene), and rs2569190 (CD14 gene).

Combinations of Polymorphic Markers of Chemokine Genes, Their Receptors and Acute Phase Protein Genes As Potential Predictors of Coronary Heart Diseases.

Atherosclerosis, the main factor in the development of coronary heart diseases (CHD), is an inflammatory response to endothelial layer damage in the arterial bed. We have analyzed the association between CHD and the polymorphic markers of genes that control the synthesis of proteins involved in the processes of adhesion and chemotaxis of immunocompetent cells: rs1024611 (-2518A>G, CCL2 gene), rs1799864 (V64I, CCR2 gene), rs3732378 (T280M, CX3CR1 gene), rs1136743 (A70V, SAA1 gene), and rs1205 (2042C>T, CRP gene) in 217 patients with CHD and 250 controls. Using the Monte Carlo method and Markov chains (APSampler), we revealed a combination of alleles/genotypes associated with both a reduced and increased risk of CHD.

[Role of PLAT, PKHD1L1, STK38L and TEAD1 genes Alu-polymorphism for longevity].

The distribution of allele and genotype frequencies of Alu(I/D)-polymorphic sites in PLAT (TPA25), PKHD1L1 (Yb8AC702), STK38L (Ya5ac2145) и TEAD1 (Ya5ac2013) genes was first characterized in the ethnically homogeneous group (Tatars from the Republic of Bashkortostan, Russia), and was established (found) the association of each gene polymorphism with age. The study group consisted of 1580 unrelated individuals aged between 21 and 109 years, including 204 long-livers. It was found that STK38L*I/D genotype had positive association with longevity in the total group (OR=1,016, p=0,034).

Genotype/allelic combinations as potential predictors of myocardial infarction.

In order to find new informative predictors of myocardial infarction, we performed an analysis of genotype frequencies of polymorphic markers of SELE (rs2076059, 3832T > C), SELP (rs6131, S290 N), SELL (rs1131498, F206L), ICAM1 (rs5498, K469E), VCAM1 (rs3917010, c.928 + 420A > C), PECAM1 (rs668, V125L), VEGFA (rs35569394, -2549(18)I/D), CCL2 (rs1024611, -2518A > G), NOS3 (rs1799983, E298D), and DDAH1 (rs669173, c.303 + 30998A > G) genes in the group of Russian men with myocardial infarction (N = 315) and the control group of corresponding ethnicity, gender, and age (N = 286).

Variants of the Coagulation and Inflammation Genes Are Replicably Associated with Myocardial Infarction and Epistatically Interact in Russians.

Background: In spite of progress in cardiovascular genetics, data on genetic background of myocardial infarction are still limited and contradictory. This applies as well to the genes involved in inflammation and coagulation processes, which play a crucial role in the disease etiopathogenesis.

Methods And Results: In this study we found genetic variants of TGFB1, FGB and CRP genes associated with myocardial infarction in discovery and replication groups of Russian descent from the Moscow region and the Republic of Bashkortostan (325/185 and 220/197 samples, correspondingly).

The CXCR2 Gene Polymorphism Is Associated with Stroke in Patients with Essential Hypertension.

Hypertension is the major risk factor for stroke, and genetic factors contribute to its development. Inflammation has been hypothesized to be the key link between blood pressure elevation and stroke. We performed an analysis of the association between inflammatory mediator gene polymorphisms and the incidence of stroke in patients with essential hypertension (EH).

Polymorphisms of inflammatory markers and risk of essential hypertension in Tatars from Russia.

Essential hypertension (EH) is a common disease with a clear genetic component. Inflammation and endothelial dysfunction play a prominent role in the development of persistent blood pressure elevation. The aim of the current study was to detect an association between EH and polymorphic markers in genes encoding for molecules involved in the control of intercellular interactions during the inflammation process.