SREBF1c and SREBF2 gene polymorphisms are associated with acute coronary syndrome and blood lipid levels in Mexican population

Abstract

Aim It 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 methods A 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. Results Under different models, the SREBF1c rs2297508 (OR = 1.50, pC Res = 0.03), SREBF1c rs11656665 (OR = 1.35, pC Dom = 0.02 and OR = 1.26, pC Add = 0.02) and SREBF2 rs2228314 (OR = 1.78, pC Res = 0.03, OR = 1.27, pC Add = 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, pC Co-dom = 0.001, OR = 0.66, pC Dom = 0.003, OR = 0.57, P Res = 0.003 and OR = 0.71, pC Add = 0.001). There was a statistically significant association of both SREBF1c rs11656665 and rs11868035 polymorphisms with plasma triglyceride levels. Conclusions In 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.

Identification of foam cell biomarkers by microarray analysis

“…Thus, SREBP-2 gene activation leads to enhanced cholesterol uptake and biosynthesis [8]. In addition, SREBF-2 variants were associated with premature CAD [9]. Seung-soon Im et al found that SREBP- 1a not only activates genes required for lipogenesis in macrophages but also the gene encoding Nlrp1a, which is a core inflammasome component [10]; SREBP2 with SREBP cleavage activating protein (SREBP cleavage activating protein, SCAP) formed SCAP-SREBP2 complex, which was required for optimal activation of the NLRP3 inflammasome both in vitro and in vivo [11], promote local inflammatory response in arterial wall.…”

A systematic review and meta-analysis of observational studies on the effects of epigenetic factors on serum triglycerides

“…SREBF-1a modulates the expression of cholesterol and fatty acid biosynthesis genes, andSREBF-1c regulates the expression of fatty acid, phospholipid, and TG biosynthetic genes. Studies demonstrated that variation in lipid profiles could be related to these proteins (32,33). According to the current literature, the level of methylation at three loci of SREBF1 gene including: cg11024682 (9,12,14,15,(23)(24)(25), cg20544516 (15) and cg08129017 ( 14) has significant and positive association with serum TG level.…”

Effect of high NEFA concentration on lipid metabolism disorders in hepatocytes based on lipidomics

“…In recent years, multiple studies have demonstrated the involvement of the sterol regulatory element-binding transcription factor (SREBF-1c) in modulating triglyceride and cholesterol levels ( Guo et al, 2014 ; Vargas-Alarcon et al, 2019 ). SREBF-1c regulates the expression of genes involved in the biosynthesis of fatty acids, phospholipids, and triglycerides ( Shimano et al, 1997 ).…”