Wang Long, Jing Jinjin, Fu Qianxi, Tang Xiaojun, Su Li, Wu Shishi, Li Ge, Zhou Li
Department of Epidemiology, the Innovation Center for Social Risk Governance in Health, School of Public Health and Management, Chongqing Medical University, Chongqing, 400016, China.
Department of Cardiology, the Second Affiliated Hospital of Chongqing Medical University, Chongqing, 400010, China.
Lipids Health Dis. 2015 May 19;14:46. doi: 10.1186/s12944-015-0043-0.
Recent genome-wide association studies (GWAS) have identified the variants near TRIB1 gene affecting blood lipid levels. However, the association between the reported variants and risk of coronary heart disease (CHD) was not confirmed.
We conducted two independent case-control studies. The first study consisted of 300 CHD patients and 300 controls and the second study had 1,332 CHD patients and 2,811 controls. The genotypes of two variants rs3201475 and rs17321515 in TRIB1 were determined by TaqMan assay. The dual-luciferase reporter assay was performed for evaluating the function of the SNP rs3201475.
The statistical analysis indicated that single nucleotide polymorphism (SNP) rs17321515 was replicated to be associated with triglyceride (TG) level, which was also significantly associated with CHD risk when using the stratified analysis after adjusting for conventional risk factors. Compared with GG genotype, AA carriers of SNP rs17321515 had higher risk in males (odds ratio (OR)=1.28, 95%CI=1.01-1.61; P=0.03) and smokers (OR=1.41, 95%CI=1.09-1.88; P=0.01). We did not find significantly association between genotypes of rs3201475 and CHD risk. In addition, no significant difference was found in the luciferase activity assay of SNP rs3201475.
Our findings indicated that SNP rs17321515 is significantly associated with plasma TG level and the increasing risk of CHD among males and smokers in Chinese, whereas there is no positive association between SNP rs3201475 and CHD risk. Smoking could modify the effects of TRIB1 on CHD risk.
近期全基因组关联研究（GWAS）已鉴定出TRIB1基因附近影响血脂水平的变异。然而，所报道的变异与冠心病（CHD）风险之间的关联尚未得到证实。
我们进行了两项独立的病例对照研究。第一项研究包括300例冠心病患者和300例对照，第二项研究有1332例冠心病患者和2811例对照。通过TaqMan分析确定TRIB1基因中两个变异rs3201475和rs17321515的基因型。采用双荧光素酶报告基因分析评估单核苷酸多态性（SNP）rs3201475的功能。
统计分析表明，单核苷酸多态性（SNP）rs17321515被重复验证与甘油三酯（TG）水平相关，在调整传统危险因素后进行分层分析时，其也与冠心病风险显著相关。与GG基因型相比，SNP rs17321515的AA携带者在男性中风险更高（优势比（OR）=1.28，95%置信区间（CI）=1.01 - 1.61；P = 0.03），在吸烟者中风险更高（OR = 1.41，95%CI = 1.09 - 1.88；P = 0.01）。我们未发现rs3201475基因型与冠心病风险之间存在显著关联。此外，SNP rs3201475的荧光素酶活性分析未发现显著差异。
我们的研究结果表明，SNP rs17321515与中国男性和吸烟者的血浆TG水平及冠心病风险增加显著相关，而SNP rs3201475与冠心病风险之间无正相关。吸烟可能改变TRIB1对冠心病风险的影响。
