Abstract
BackgroundHyperlipidemia is a major risk factor for coronary artery disease (CAD). The current study was designed to explore the possible correlation between single nucleotide polymorphisms (SNPs) in the lipid homeostasis regulatory genes F-box and WD repeat domain–containing 7 (FBXW7) and sterol regulatory element-binding proteins (SREBPs) with CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China.ResultsIn the Uygur Chinese population, rs9902941 in SREBP-1 and rs10033601 in FBXW7 were found to be associated with CAD in a recessive model (TT vs. CT + CC, P = 0.032; GG vs. AG + AA, P = 0.010, respectively), and rs7288536 in SREBP-2 was found to be associated with CAD in an additive model (CT vs. CC + TT, P = 0.045). The difference was statistically significant in the Uygur Chinese population after multivariate adjustments [Odds ratio (OR) = 1.803, 95% confidence interval (CI): 1.036~3.137, P = 0.037; OR = 1.628, 95% CI: 1.080~2.454, P = 0.020; OR = 1.368; and 95% CI: 1.018~1.837, P = 0.037, respectively]. There were also significant interactions between the above-mentioned models in the Uygur Chinese population. However, these relationships were not observed before or after multivariate adjustment in the Han Chinese population.Materials and MethodsA total of 1,312 Han Chinese (650 CAD patients and 662 controls) and 834 Uygur Chinese (414 CAD patients and 420 controls) were enrolled in this case-control study. Three SNPs (rs9902941 in SREBP-1, rs7288536 in SREBP-2 and rs10033601 in FBXW7) were selected and genotyped using the improved multiplex ligase detection reaction (iMLDR) method.ConclusionsThe results of this study indicate that variations in the lipid regulatory pathway genes FBXW7 and SREBPs (rs9902941 in SREBP-1, rs7288536 in SREBP-2 and rs10033601 in FBXW7) are associated with CAD in the Uygur Chinese population in Xinjiang, China.
Highlights
Coronary artery disease (CAD) is the most common chronic disease; it is becoming increasingly prevalent and remains the leading cause of disability and mortality throughout the world [1,2,3]
In the Uygur Chinese population, rs9902941 in sterol regulatory elementbinding proteins (SREBPs)-1 and rs10033601 in F-box and WD repeat domain–containing 7 (FBXW7) were found to be associated with coronary artery disease (CAD) in a recessive model (TT vs. CT + CC, P = 0.032; GG vs. AG + AA, P = 0.010, respectively), and rs7288536 in SREBP-2 was found to be associated with CAD in an additive model (CT vs. CC + TT, P = 0.045)
The difference was statistically significant in the Uygur Chinese population after multivariate adjustments [Odds ratio (OR) = 1.803, 95% confidence interval (CI): 1.036~3.137, P = 0.037; OR = 1.628, 95% CI: 1.080~2.454, P = 0.020; OR = 1.368; and 95% CI: 1.018~1.837, P = 0.037, respectively]
Summary
Coronary artery disease (CAD) is the most common chronic disease; it is becoming increasingly prevalent and remains the leading cause of disability and mortality throughout the world [1,2,3]. CAD is a multifactorial disease that results from both genetic and environmental risk factors. Lipid metabolism is regulated by a family of transcription factors known as sterol regulatory elementbinding proteins (SREBPs) [8]. The SREBP family controls cholesterol and lipid synthesis by activating the expression of SREBP target genes, such as fatty acid synthase, 3-hydroxy-3-methylglutarylCoA (HMG-CoA) reductase, HMG-CoA synthase, and the low-density lipoprotein (LDL) receptor [11, 12]. Hyperlipidemia is a major risk factor for coronary artery disease (CAD). The current study was designed to explore the possible correlation between single nucleotide polymorphisms (SNPs) in the lipid homeostasis regulatory genes F-box and WD repeat domain–containing 7 (FBXW7) and sterol regulatory elementbinding proteins (SREBPs) with CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China
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