Cha Erdenbat, Fu Zhen-Yan, Ma Yi-Tong, Zhu Qing, Xie Xiang, Liu Fen
Department of Cardiology, First Affiliated Hospital of Xinjiang Medical University, Urumqi, Xinjiang 830054, China.
Lipids Health Dis. 2014 Sep 9;13:147. doi: 10.1186/1476-511X-13-147.
GP78 is a membrane-anchored ubiquitin ligase mediating the degradation of 3-hydroxy-3-methyl-glutaryl-CoA coenzyme A reductase (HMGCR) and Insig-1, which was very essential for the synthesis of cholesterol process. Cholesterol levels have a causal role in the development of cardiovascular disease. The aim of the present study was to assess the association between the human gp78 gene polymorphism and coronary artery disease (CAD) in a Han and Uygur population of China.
We used two independent case-control studies: a Han population (602 CAD patients and 572 control subjects) and a Uygur population (374 CAD patients and 376 control subjects). All CAD patients and controls were genotyped for the same three single nucleotide polymorphisms (SNPs) (rs731119, rs2617849 and rs2440472) of gp78 gene by a Real-time PCR instrument.
In the Han population, for total and men, the distribution of SNP3 (rs2440472) alleles and the dominant model (AA vs AG + GG) and recessive model (GG vs AG + AA) showed a significant difference between CAD and control participants (for allele: P = 0.003 and P = 0.002, respectively; for dominant model: P = 0.041 and P = 0.026, respectively; for recessive model: p = 0.004 and p = 0.004, respectively).The significant difference in both the two models was retained after adjustment for covariates (for dominant model OR:0.760, 95% confidence interval [CI]:0.584-0.99, P = 0.042; OR:0.686, 95% CI: 0.498-0.946, P = 0.022, respectively; for recessive model OR: 1.451, 95% CI: 1.067-1.974, P = 0.018; OR: 1.789, 95% CI: 1.219-2.627, P = 0.000). Our data was also assessed via haplotype-based case-control studies. For the Han population, for total, The G-T-G haplotype in CAD was significantly higher than that in the control group (P = 0.02), and the G-C-A haplotype in CAD was significantly lower than that in the control group (P = 0.0443), And for man, the G-T-G haplotype in CAD was significantly higher than that in the control group (P = 0.0048).
The GG genotype and G allele of rs2440472 in gp78 gene could be a risk genetic marker of CAD in Han population in China.
GP78是一种膜锚定泛素连接酶，介导3-羟基-3-甲基戊二酰辅酶A还原酶（HMGCR）和Insig-1的降解，这对胆固醇合成过程非常重要。胆固醇水平在心血管疾病的发生中起因果作用。本研究的目的是评估中国汉族和维吾尔族人群中人类gp78基因多态性与冠状动脉疾病（CAD）之间的关联。
我们采用了两项独立的病例对照研究：一个汉族人群（602例CAD患者和572例对照）和一个维吾尔族人群（374例CAD患者和376例对照）。通过实时PCR仪对所有CAD患者和对照进行gp78基因相同的三个单核苷酸多态性（SNP）（rs731119、rs2617849和rs2440472）的基因分型。
在汉族人群中，总体和男性中，SNP3（rs2440472）等位基因的分布以及显性模型（AA与AG + GG）和隐性模型（GG与AG + AA）在CAD患者和对照参与者之间存在显著差异（等位基因：P分别为0.003和0.002；显性模型：P分别为0.041和0.026；隐性模型：p分别为0.004和0.004）。在调整协变量后，两个模型中的显著差异均得以保留（显性模型OR：0.760，95%置信区间[CI]：0.584 - 0.99，P = 0.042；OR：0.686，95% CI：0.498 - 0.946，P = 0.022；隐性模型OR：1.451，95% CI：1.067 - 1.974，P = 0.018；OR：1.789，95% CI：1.219 - 2.627，P = 0.000）。我们的数据还通过基于单倍型的病例对照研究进行了评估。对于汉族人群总体而言，CAD中的G-T-G单倍型显著高于对照组（P = 0.02），CAD中的G-C-A单倍型显著低于对照组（P = 0.0443），对于男性，CAD中的G-T-G单倍型显著高于对照组（P = 0.0048）。
gp78基因中rs2440472的GG基因型和G等位基因可能是中国汉族人群中CAD的风险遗传标记。
