Genetic markers of cardiac autonomic neuropathy in the Kazakh population.

BACKGROUND: Cardiac autonomic neuropathy (CAN) is a complication of diabetes mellitus (DM) that increases the risk of morbidity and mortality by disrupting cardiac innervation. Recent evidence suggests that CAN may manifest even before the onset of DM, with prediabetes and metabolic syndrome potentially serving as precursors. This study aims to identify genetic markers associated with CAN development in the Kazakh population by investigating the SNPs of specific genes. MATERIALS AND METHODS: A case-control study involved 82 patients with CAN (cases) and 100 patients without CAN (controls). A total of 182 individuals of Kazakh nationality were enrolled from a hospital affiliated with the RSE "Medical Center Hospital of the President's Affairs Administration of the Republic of Kazakhstan". 7 SNPs of genes FTO, PPARG, SNCA, XRCC1, FLACC1/CASP8 were studied. Statistical analysis was performed using Chi-square methods, calculation of odds ratios (OR) with 95% confidence intervals (CI), and logistic regression in SPSS 26.0. RESULTS: Among the SNCA gene polymorphisms, rs2737029 was significantly associated with CAN, almost doubling the risk of CAN (OR 2.03(1.09-3.77), p = 0.03). However, no statistically significant association with CAN was detected with the rs2736990 of the SNCA gene (OR 1.00 CI (0.63-1.59), p = 0.99). rs12149832 of the FTO gene increased the risk of CAN threefold (OR 3.22(1.04-9.95), p = 0.04), while rs1801282 of the PPARG gene and rs13016963 of the FLACC1 gene increased the risk twofold (OR 2.56(1.19-5.49), p = 0.02) and (OR 2.34(1.00-5.46), p = 0.05) respectively. rs1108775 and rs1799782 of the XRCC1 gene were associated with reduced chances of developing CAN both before and after adjustment (OR 0.24, CI (0.09-0.68), p = 0.007, and OR 0.43, CI (0.22-0.84), p = 0.02, respectively). CONCLUSION: The study suggests that rs2737029 (SNCA gene), rs12149832 (FTO gene), rs1801282 (PPARG gene), and rs13016963 (FLACC1 gene) may be predisposing factors for CAN development. Additionally, SNPs rs1108775 and rs1799782 (XRCC1 gene) may confer resistance to CAN. Only one polymorphism rs2736990 of the SNCA gene was not associated with CAN.

Association of Polymorphism rs2736990 of the α-Synuclein Gene with Metabolic Syndrome Among the Population of Kazakhstan with Arterial Hypertension.

Background: The prevalence of metabolic syndrome (MetS) in Kazakhstan reaches 40%. The presence of an association between certain genetic markers and the development of MetS will allow more accurately determining the cardiovascular risk for patients with hypertension and personalizing preventive recommendations. Methods: The purpose of the study was to investigate the presence of an associative relationship between various polymorphisms of the α-synuclein gene and the development of MetS in Kazakh people with high blood pressure. Four hundred twenty-six patients were examined [age 49.5 (interquartile range 42.5-56), men 209 (49.1%), women 217 (50.9%)]. Standard clinical and laboratory methods were used. AutoMate Express™ and OpenArray technologies were used for DNA extraction and further genotyping. Patients with MetS made up the ms+ group, those without MetS-the ms- group. Results: In the examined patients, four polymorphisms of the α-synuclein gene were identified: rs356219, rs2736990, rs11931074, and rs2737029. According to the results of statistical analysis, the frequency and risk of developing MetS did not depend on different alleles and inheritance types of polymorphisms rs356219 and rs11931074. The minor allele of polymorphism rs2737029 exhibits a higher frequency in patients with arterial hypertension accompanied by MetS, although the specific model of inheritance remains to be conclusively determined. Conclusions: In carriers of the minor allele of polymorphism rs2736990, the risk of MetS increases 1.3 times, regardless of age and gender [odds ratio (95% confidence interval) = 1.36 (1.01-1.82), P < 0.05], the inheritance model is log-additive.

Evolution of the search for a common mechanism of congenital risk of coronary heart disease and type 2 diabetes mellitus in the chromosomal locus 9p21.3.

9.21.3 chromosomal locus predisposes to coronary heart disease (CHD) and type 2 diabetes mellitus (DM2), but their overall pathological mechanism and clinical applicability remain unclear. The review uses publications of the study results of 9.21.3 chromosomal locus in association with CHD and DM2, which are important for changing the focus of clinical practice. The eligibility criteria are full-text articles published in the PubMed database (MEDLINE) up to December 31, 2022. A total of 56 publications were found that met the inclusion criteria. Using the examples of the progressive stages in understanding the role of the chromosomal locus 9p.21.3, scientific ideas were grouped, from a fragmentary study of independent pathological processes to a systematic study of the overall development of CHD and DM2. The presented review can become a source of new scientific hypotheses for further studies, the results of which can determine the general mechanism of the congenital risk of CHD and DM2 and change the focus of clinical practice.

Polymorphic genetic markers and how they are associated with clinical and metabolic indicators of type 2 diabetes mellitus in the Kazakh population.

BACKGROUND: Type 2 diabetes mellitus is a serious public health problem worldwide. The aim of the study was to analyze the relationship of eight polymorphic gene variants with the development of clinical-metabolic rates of type 2 diabetes mellitus inside Kazakh population. MATERIALS AND METHODS: 139 patients with type 2 diabetes mellitus and 100 patients in the control group were examined. Genotyping of polymorphisms of candidate genes was carried out on a next generation QuantStudio 12 K Flex unit. RESULTS: Gene TCF7L2 locus rs7901695 and rs7903146, gene KCNQ1 locus rs2237892, rs7756992, and gene CDKAL1 locus rs7754840 demonstrated statistically significant associations with glucose metabolism, lipid profile and body mass index (BMI) in type 2 DM inside the population. Statistically significant difference in anthropometric and biochemical measures of rs17584499, rs4712523 and rs163184 has not been revealed. CONCLUSIONS: Genetic polymorphisms that influence pancreatic gland beta-cells insulin release and secretion associate with metabolic and anthropometric measures definitive for type 2 DM in Kazakh population.

Association of 3 single nucleotide polymorphisms of the eighth chromosome with remodeling of the myocardium and carotid arteries in the Kazakh population.

ABSTRACT: Cardiovascular diseases are one of the key health issues in Kazakhstan. According to the WHO, the prevalence of arterial hypertension (AH) was 28% in males and 25% in females in 2015, which puts up vastly to premature mortality from non-communicable diseases.The search for genetic features of target organ lesions processes in AH is relevant. The goal of this study was to search for the genetic markers of myocardial remodeling (MR) and carotid artery remodeling (CAR).A total of 866 hypertensive individuals were recruited in Nur-Sultan, Kazakhstan. Their blood was genotyped for 9 single nucleotide polymorphisms (SNPs) of the eighth chromosome to find an association with remodeling. The analysis was carried out in the group pairs (control and CAR, control and MR, and control and CAR and MR). The genotype-phenotype association was assessed using 5 different inheritance models: dominant, codominant, recessive, overdominant, and log-additive.Statistically significant results were found for 3 SNPs (rs2407103, rs11775334, rs2071518) which minor alleles enlarged risks of MR and CAR in AH in the studied population. Three polymorphisms have previously been associated with АН and some other traits like pulse pressure and blood glucose in other ethnic populations: rs2407103 - in Afro-American population, rs11775334 - in the European population, rs2071518 is well studied in various ethnic populations (European, South Asian, Afro-American, Hispanic, East Asian).