In recent studies, the T-1131C variant of apolipoprotein A5 (APOA5) gene was found to confer a risk for metabolic syndrome (MS). Here we determined four haplotype-tagging polymorphisms (T-1131C, IVS3+ Show more
In recent studies, the T-1131C variant of apolipoprotein A5 (APOA5) gene was found to confer a risk for metabolic syndrome (MS). Here we determined four haplotype-tagging polymorphisms (T-1131C, IVS3+G476A, T1259C, and C56G), and studied the distribution of the naturally occurring major haplotype profiles in MS. A total of 343 MS patients and 284 controls were genotyped using PCR-RFLP methods. Both in MS and control groups, we confirmed the already known association of -1131C, IVS3+473A and 1259C minor alleles with elevated triglyceride levels. The prevalence of the APOA5*2 haplotype (the combination of T-1131C, IVS3+G476A and T1259C SNPs) was 13.1% in MS patients, and 4.9% in controls (p<0.001); multiple logistic regression analysis revealed that this haplotype confers risk for the development of MS (OR=2.880; 95% CI: 1.567-5.292; p=0.001). We also observed a gender effect: in males a more prominent degree of susceptibility was found. Contrary to the APOA5*2 haplotype, the prevalence rate of APOA5*4 (determined by the T-1131C SNP alone) did not differ between MS patients and controls. We identified a novel haplotype, designated here as APOA5*5 (1259C allele alone); which appears to be protective against MS. Our results refined the role of SNP T-1131C in the development of MS. The susceptibility nature of this SNP is limited to the APOA5*2 haplotype, while in APOA5*4 haplotype it did not confer a risk for the disease. In addition, as our current data suggest, the novel APOA5*5 haplotype can confer protection against MS. Show less
Metabolic syndrome consists of multiple risk factors that are increasing the cardiovascular mortality. The T-1131C variant of the apolipoprotein A5 gene, associated with increased triglycerides, has b Show more
Metabolic syndrome consists of multiple risk factors that are increasing the cardiovascular mortality. The T-1131C variant of the apolipoprotein A5 gene, associated with increased triglycerides, has been found to confer risk for cardiovascular diseases and metabolic syndrome. Because other naturally occurring variants of the gene also correlate with elevated triglycerides, the possible role of 2 common variants, the IVS3+G476A and T1259C, with metabolic syndrome was investigated. A total of 213 metabolic syndrome patients and 142 healthy controls were genotyped by polymerase chain reaction-restriction fragment length polymorphism. Serum triglycerides were increased in carriers compared with non-carriers in both groups (p<0.001); serum cholesterol levels were similar in all genotypes. The IVS3+476A allele frequency was increased in metabolic syndrome patients compared with controls (8.05 vs 2.47%; p<0.05), whereas the 1259C allele frequency did not differ between the groups. Multiple logistic regression analyses adjusted for age, gender, serum total cholesterol, acute myocardial infarction and stroke revealed that the IVS3+476A variant confers risk for development of metabolic syndrome (odds ratio =3.529, 95% confidence interval 1.308-9.029, p=0.009), but the 1259C allele had no such an effect. Carrying the IVS3+473A allele is associated with elevated triglycerides and confers risk for development of metabolic syndrome, a combination that represents increased risk for development of atherogenic vascular diseases. Show less