中国新疆汉族和维吾尔族人群中脂质调节通路基因FBXW7和SREBPs的遗传变异与冠状动脉疾病的关联
Association of genetic variations in the lipid regulatory pathway genes FBXW7 and SREBPs with coronary artery disease among Han Chinese and Uygur Chinese populations in Xinjiang, China.
作者信息
Abudesimu Asiya, Adi Dilare, Siti Dilixiati, Xie Xiang, Yang Yi-Ning, Li Xiao-Mei, Wang Ying-Hong, Wang Yong-Tao, Meng Ya-Jie, Liu Fen, Chen Bang-Dang, Ma Xiang, Fu Zhen-Yan, Ma Yi-Tong
机构信息
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, PR China.
Xinjiang Key Laboratory of Cardiovascular Disease, Clinical Medical Research Institute of First Affiliated Hospital of Xinjiang Medical University, Urumqi, PR China.
出版信息
Oncotarget. 2017 Sep 19;8(50):88199-88210. doi: 10.18632/oncotarget.21082. eCollection 2017 Oct 20.
BACKGROUND
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 element-binding proteins (SREBPs) with CAD among Han Chinese and Uygur Chinese populations in Xinjiang, China.
RESULTS
In 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, = 0.032; GG vs. AG + AA, = 0.010, respectively), and rs7288536 in SREBP-2 was found to be associated with CAD in an additive model (CT vs. CC + TT, = 0.045). The difference was statistically significant in the Uygur Chinese population after multivariate adjustments [Odds ratio (OR) = 1.803, 95% confidence interval (CI): 1.0363.137, = 0.037; OR = 1.628, 95% CI: 1.0802.454, = 0.020; OR = 1.368; and 95% CI: 1.018~1.837, = 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 METHODS
A 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.
CONCLUSIONS
The 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.
背景
高脂血症是冠状动脉疾病（CAD）的主要危险因素。本研究旨在探讨中国新疆汉族和维吾尔族人群中，脂质稳态调节基因F-box和含WD重复结构域7（FBXW7）以及固醇调节元件结合蛋白（SREBPs）中的单核苷酸多态性（SNP）与CAD之间可能存在的相关性。
结果
在维吾尔族人群中，SREBP-1中的rs9902941和FBXW7中的rs10033601在隐性模型中与CAD相关（TT与CT + CC相比，P = 0.032；GG与AG + AA相比，P = 0.010），SREBP-2中的rs7288536在加性模型中与CAD相关（CT与CC + TT相比，P = 0.045）。在进行多变量调整后，维吾尔族人群中的差异具有统计学意义[比值比（OR）= 1.803，95%置信区间（CI）：1.0363.137，P = 0.037；OR = 1.628，95% CI：1.0802.454，P = 0.020；OR = 1.368；95% CI：1.018~1.837，P = 0.037]。在维吾尔族人群中，上述模型之间也存在显著的相互作用。然而，在汉族人群中，无论多变量调整前后均未观察到这些关系。
材料与方法
本病例对照研究共纳入1312名汉族人（650例CAD患者和662例对照）和834名维吾尔族人（414例CAD患者和420例对照）。选择了三个SNP（SREBP-1中的rs9902941、SREBP-2中的rs7288536和FBXW7中的rs10033601），并使用改进的多重连接检测反应（iMLDR）方法进行基因分型。
结论
本研究结果表明，脂质调节途径基因FBXW7和SREBPs（SREBP-1中的rs9902941、SREBP-2中的rs7288536和FBXW7中的rs10033601）的变异与中国新疆维吾尔族人群中的CAD相关。
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