Résumé
SUMMARY OBJECTIVE: The aim of this study was to determine frequency and associations between APOA5 c.56C>G, −1131T>C, c.553G>T, and APOC3 −482C>T and SstI gene polymorphisms with hypertriglyceridemia. METHODS: Under a case-control study model, 135 hypertriglyceridemic and 178 normotriglyceridemic control participants were recruited. Polymerase chain reaction and restriction fragment length polymorphism methods were utilized for genotyping. Statistical calculations were performed by comparing allele and genotype frequencies between groups. Clinical characteristics were compared between groups and intra-group genotypes. RESULTS: APOC3 gene −482C>T and SstI polymorphic genotypes and allele frequencies were significantly higher in hypertriglyceridemic group (genotype frequencies, p=0.035, p=0.028, respectively). Regression analysis under unadjusted model confirmed that APOC3 −482C>T and SstI polymorphisms were significantly contributing to have hypertriglyceridemia (p=0.02, odds ratio [OR]=1.831 (95% confidence interval [CI] 1.095-3.060); p=0.04, OR=1.812 (1.031-3.183), respectively). APOA5 c.56C>G was in complete linkage disequilibrium with APOA5 c.553G>T polymorphism (D'=1). CONCLUSION: For the first time in a population sample from Turkey, among the five polymorphisms of APOA5 and APOC3 genes investigated, APOC3 −482C>T and SstI polymorphisms were associated with elevated serum TG levels, while APOA5 c.56C>G, −1131T>C, and c.553G>T polymorphisms were not.
Résumé
Recently, the relationship between hypertriglyceridemia (HTG) and atherosclerosis has become the new research focus, as HTG increases the lipids exchange between lipoproteins mediated by cholesteryl ester transfer protein (CETP), increases the concentrations of triglyceride-rich lipoproteins through the apolipoprotein C III and increases the high platelet CD40L expressions. In this paper, we briefly introduced the related drugs and focus on the latest epidemiological survey data and the molecular mechanisms of HTG accelerating atherosclerosis. Our purpose is to further clarify the important role and significance of triglycerides in the development of atherosclerosis, and provide a new theoretical basis for the prevention and treatment of atherosclerotic cardiovascular disease.
Résumé
BACKGROUND: Hypertriglyceridemia and hypercholesterolemia have been associated with atherosclerosis, myocaridal infarction, and premature death. However, the causes of hyperlipidemia are not well understood. Variations in apolipoprotein C-III (apo C-III) are candidate for contributing to the occurrence of hypertriglyceridemia. A genetically variant form of human apo C-III promoter, containing five single base pair changes, has been shown that it seems to be associated with hypertriglyceridemia. Especially, the loss of insulin regulation was mapped to polymorphic sites at -482 and -455, which fall within an insulin response element. METHODS: We studied 146 subjects with hyperlipidemia and also had 94 controls. Screening for mutations at codon -482 and -455 of apo C-III promoter were carried out by PCR-RFLP analyses. RESULTS: 1) In the codon -482 site of the patient group, the genotype frequency of T/T homozygote was higher than in the control group, whereas the frequency of T/C heterozygote and C/C homozygote were lower. 2) Serum triglyceride related to genotype shows positive correlation trend with freguency of -482 T allele and -455 C allele, but has not stastistical significancy. 3) In complete mutated groups of both -482 T/T and -455 C/C in hyperlipidemia patients, serum triglyceride and fasting blood glucose are higher than in wild type groups of both -482 C/C and -455 T/T. CONCLUSION: We suggest that variations of the promoter of apolipoprotein C-III may be a genetic marker in patients with hyperlipidemia.