He Mei-An, Zhang Xiaomin, Wang Jing, Cheng Longxian, Zhou Li, Zeng Hesong, Wang Feng, Chen Ying, Xu Zengguang, Wei Qingyi, Hu Frank B, Wu Tangchun
Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong University of Science and Technology, Wuhan, Hubei, China.
Cell Stress Chaperones. 2008 Summer;13(2):231-8. doi: 10.1007/s12192-008-0025-5. Epub 2008 Mar 5.
High levels of circulating heat shock protein 60 (Hsp60) and antibody to human Hsp60 have been associated with greater risk of coronary heart disease (CHD) in several studies, but associations between polymorphisms of the hsp60 gene and CHD risk have not been investigated.
By resequencing DNA from 30 unrelated Han Chinese and using HapMap Phase I Chinese data of hsp60 gene, we selected four tagging single nucleotide polymorphisms (tagSNPs) named rs2340690, rs788016, rs2305560, and rs2565163, and determined their frequencies in 1,003 Chinese CHD patients and 1,003 age- and sex-frequency-matched controls. Furthermore, we used PHASE 2.0 software to reconstruct haplotypes and logistic regression to control for potential confounders in multivariate analyses.
We found 13 SNPs in hsp60 gene (including four novel SNPs) in Han Chinese subjects. Our results showed no significant differences in four selected SNPs in patients with CHD and controls after adjusting for other conventional risk factors and stratifying by age, sex, smoking status, past history of hypertension and DM; however, our results showed that subjects with the GCTC haplotype had about twofold higher risk of CHD than those with the GTTC haplotype (OR = 1.91, 95%CI: 1.26-2.89, P = 0.002).
Our results suggest that the GCTC haplotype in the hsp60 gene is significantly associated with higher CHD risk in a Chinese population.
在多项研究中，循环热休克蛋白60（Hsp60）和抗人Hsp60抗体水平升高与冠心病（CHD）风险增加有关，但hsp60基因多态性与CHD风险之间的关联尚未得到研究。
通过对30名无亲缘关系的汉族人DNA进行重测序，并使用Hsp60基因的HapMap一期中国数据，我们选择了4个标签单核苷酸多态性（tagSNP），分别命名为rs2340690、rs788016、rs2305560和rs2565163，并确定了它们在1003例中国CHD患者和1003例年龄及性别频率匹配的对照中的频率。此外，我们使用PHASE 2.0软件重建单倍型，并使用逻辑回归在多变量分析中控制潜在混杂因素。
我们在汉族受试者的hsp60基因中发现了13个SNP（包括4个新的SNP）。我们的结果显示，在调整其他传统风险因素并按年龄、性别、吸烟状况、高血压和糖尿病既往史分层后，CHD患者和对照中4个选定的SNP没有显著差异；然而，我们的结果显示，具有GCTC单倍型的受试者患CHD的风险比具有GTTC单倍型的受试者高约两倍（OR = 1.91，95%CI：1.26 - 2.89，P = 0.002）。
我们的结果表明，hsp60基因中的GCTC单倍型与中国人群中较高的CHD风险显著相关。
