Association of Interleukin-10 -592 C > A gene polymorphism with coronary artery disease: A case-control study and meta-analysis.

BACKGROUND: Coronary-artery-disease (CAD) is the leading cause of death worldwide, and hence there is a need to identify reliable markers for identifying individuals at high risk of developing CAD. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that is associated with an increased risk of developing both atherosclerosis and acute coronary events. The study aimed to explore the association of a genetic variant in IL-10 with the risk of developing CAD and the severity of the disease. To further explore, a systematic review and meta-analysis was performed. The cumulative results of the relationship between IL and 10 -592 C > A polymorphism and CAD in Iranian population have also been presented. METHODS: In this cross sectional study, a total of 948 individuals including 307 healthy controls and 641 patients that among cases, four hundred and fifty-five of the patients had > 50% stenosis (angiogram positive group) and 186 patients had < 50% stenosis (angiogram negative group) were recruited from the Mashhad-Stroke and Heart-Atherosclerotic-Disorders cohort. Genotyping for the IL-10 -592 C > A polymorphism was performed using a PCR-RFLP technique, and statistical analysis undertaken by univariate and multivariate analyses. PubMed, Google Scholar and Scopus were searched for papers related to this polymorphism up to October 2019. The Meta-analysiswas done based on the random effect model using a Meta-analysis. RESULTS: In our study, the frequency of the variant A allele of the IL-10 -592 C > A was significantly higher in CAD patients than the control group (P value = 0.043). Moreover, subjects carrying AA genotype had a significantly higher risk of CAD (OR: 1.8, 95%CI: 1.04-3.16), p = 0.03), compared to those with the wild type genotype. The results of meta-analysis of 9336 cases and 8461 controls did not also show any significant association between IL and 10 -592 C > A and CAD in dominant and recessive genetic models but only in co-dominant model when fix effect was applied. CONCLUSION: Although our research findings support a significant association of genetic polymorphism in the IL10 gene with cardiovascular diseases, this finding cannot be confirmed in meta-analysis. Further functional analysis and evaluation of this marker in a multicenter setting are needed to establish its value as a risk stratification marker.

Dyslipidemia and cardiovascular disease risk among the MASHAD study population.

INTRODUCTION: Dyslipidemia may be defined as increased levels of serum total cholesterol (TC), low-density lipoprotein cholesterol (LDL-C), triglycerides (TG), or a decreased serum high-density lipoprotein cholesterol (HDL-C) concentration. Dyslipidemia is an established risk factor for cardiovascular disease (CVD). We aimed to investigate the association of dyslipidemia and CVD events among a population sample from Mashhad, in northeastern Iran. MATERIAL AND METHODS: This prospective cohort study comprised a population of 8698 men and women aged 35-65 years who were recruited from the Mashhad Stroke and Heart Atherosclerotic Disorder (MASHAD) study. Socioeconomic and demographic status, anthropometric parameters, laboratory evaluations, lifestyle factors, and medical history were gathered through a comprehensive questionnaire and laboratory and clinical assessment for all participants. Cox regression model and 95% confidence interval (CI) were used to evaluate the association of dyslipidemia and its components with CVD incidence. RESULTS: After 6 years of follow-up, 233 cases of CVD (including 119 cases of unstable angina [US], 74 cases of stable angina [SA], and 40 cases of myocardial infarction [MI]) were identified in the study population. Unadjusted baseline serum LDL-C, TC, and TG levels were positively associated with the risk of total CVD events among the entire population (HR: 1.54, 95% CI: 1.19-2; P-value< 0.01; HR: 1.53; 95% CI: 1.18-1.98; P < 0.01; HR: 1.57; 95% CI: 1.27-2.03; P < 0.01, respectively). However, after adjusting for confounding factors (age, body mass index [BMI], family history of CVD, smoking status [non-smoker, ex-smoker and current smoker], lipid lowering drug treatment, anti-hypertensive drug treatment, hypertension, healthy eating index [HEI], total energy intake, and presence of diabetes mellitus), a significant direct association only remained between TC and MI risk in men (HR: 2.71; 95%CI: 1.12-6.57; P-value< 0.05). CONCLUSION: In the present study, TC baseline level was significantly associated with the risk of MI among men.

Association of heat shock protein70-2 (HSP70-2) gene polymorphism with coronary artery disease in an Iranian population.

BACKGROUND: Coronary artery disease (CAD) is an inflammatory process and a major cause of mortality and morbidity. The (heat shock protein70-2) HSP70-2 gene is reported to be associated with coronary artery disease possibly by affecting the regulation of pro-inflammatory cytokines such as TNF-α. The association between CAD and the HSP70-2 gene +1267A>G polymorphism has been studied in some populations but there are no data about this association in the Iranian population. AIM: We have investigated the association between the HSP70-2 gene +1267A>G polymorphism and angiographically defined CAD within an Iranian population. METHODS: We determined the presence of the HSP70-2 gene +1267A>G polymorphism in 628 patients with CAD and 307 healthy individuals using PCR-RFLP. Of the patients, 433 (68%) had >50% stenosis (CAD+) and the remaining 195 patients had <50% stenosis (CAD-), based on coronary angiography. Angiogram positive patients were subdivided into three groups: those with single (n=113), double (n=134), and triple vessels (n=186) disease. RESULTS: A significant higher frequency of AG+GG genotypes (G allele carriers) was observed in angiogram positive and angiogram negative groups compared to controls in a dominant analysis model of the HSP70-2 gene +1267A>G position (51.2 vs. 43.2, P=0.002, OR=1.37) (51.0 vs. 43.2, P=0.01, OR=1.37). The allele frequency of the HSP70-2 G was also significantly higher in angiogram positive and angiogram negative groups compared to the control group (51.2 vs. 43.2, P=0.002, OR=1.37) (51.0 vs. 43.2, P=0.01, OR=1.37). CONCLUSION: These results suggest that HSP70-2 +1267 polymorphism may influence the risk of CAD in Iranian population, however further studies are needed to clarify the role of other HSP70-2 gene polymorphisms in the pathogenesis of the CAD.