Abstract
AimIt has recently been reported that the sterol regulatory element-binding transcription factors (SREBF-1c, and -2) contribute to the variation in the plasma lipids levels, which have an important role in the atherosclerotic plaque development. The aim of the present study was to evaluate whether the SREBF1c and SREBF2 gene single nucleotide polymorphisms (SNPs) are associated with plasma lipids levels and ACS susceptibility in a case-control association study.Material and methodsA case-control study was carried out in 625 patients with ACS (82% men and 18% women, with a mean age of 57.97 ± 10.5 years) and 700 healthy controls (66% men and 34% women, with a mean age of 54.37 ± 7.65 years). The sample size was calculated for a statistical power of 80%. We genotyped three SREBF1c (rs2297508, rs11656665 and rs11868035) and three SREBF2 (rs2267439, rs2267443, and rs2228314) gene polymorphisms by 5’ exonuclease TaqMan assays. The associations were evaluated by logistic regression under the co-dominant, dominant, recessive, over-dominant and additive inheritance models. The contribution of the genotypes on the plasma lipids levels was evaluated by Student’s t-test.ResultsUnder different models, the SREBF1c rs2297508 (OR = 1.50, pCRes = 0.03), SREBF1c rs11656665 (OR = 1.35, pCDom = 0.02 and OR = 1.26, pCAdd = 0.02) and SREBF2 rs2228314 (OR = 1.78, pCRes = 0.03, OR = 1.27, pCAdd = 0.04) SNPs were associated with higher risk of ACS. On the other hand, the SREBF1c rs11868035 SNP was associated with lower risk of ACS (OR = 0.49, pCCo-dom = 0.001, OR = 0.66, pCDom = 0.003, OR = 0.57, PRes = 0.003 and OR = 0.71, pCAdd = 0.001). There was a statistically significant association of both SREBF1c rs11656665 and rs11868035 polymorphisms with plasma triglyceride levels.ConclusionsIn summary, our data suggest the association of the SREBF1c and SREBF2 SNPs with risk of developing ACS and with triglyceride levels in a Mexican population.
Highlights
The acute coronary syndrome (ACS) is an important consequence of both atherosclerosis and abnormalities in lipid levels, constitutes a worldwide public health problem
The Sterol regulatory element binding transcription factor 1c (SREBF1c) rs2297508 (OR = 1.50, pCRes = 0.03), SREBF1c rs11656665 (OR = 1.35, pCDom = 0.02 and odds ratios (ORs) = 1.26, pCAdd = 0.02) and Sterol regulatory element binding transcription factor 2 (SREBF2) rs2228314 (OR = 1.78, pCRes = 0.03, OR = 1.27, pCAdd = 0.04) Single nucleotide polymorphism (SNP) were associated with higher risk of ACS
Our data suggest the association of the SREBF1c and SREBF2 SNPs with risk of developing ACS and with triglyceride levels in a Mexican population
Summary
The acute coronary syndrome (ACS) is an important consequence of both atherosclerosis and abnormalities in lipid levels, constitutes a worldwide public health problem. Several studies have indicated that the sterol regulatory element-binding transcription factors (SREBF-1a, -1c, and -2) contribute to the variation of cholesterol, triglycerides, high-density lipoprotein-cholesterol (HDL-C), and lowdensity lipoprotein-cholesterol (LDL-C) levels [4,5,6]. These factors are partly responsible for the development of some diseases, such as type 2 diabetes mellitus (T2DM), schizophrenia, ischemia stroke, coronary artery disease, and hypercholesterolemia [7,8,9,10,11,12]. SREBF-1a stimulates the expression of both cholesterol and fatty acid biosynthesis genes, whereas SREBF-1c controls the expression of fatty acid, phospholipid and triglyceride biosynthetic genes [13,14,15,16,17]
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