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Genetic variation in heat shock protein 60 gene and coronary heart disease in China: tagging-SNP haplotype analysis in a case-control study

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Cell Stress and Chaperones Aims and scope

Abstract

Background

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.

Methods

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.

Results

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).

Conclusions

Our results suggest that the GCTC haplotype in the hsp60 gene is significantly associated with higher CHD risk in a Chinese population.

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Abbreviations

BMI:

body mass index

CHD:

coronary heart disease

CIs:

confidence intervals

FBG:

fasting blood glucose

Hsp60:

heat shock protein 60

LD:

linkage disequilibrium

MAF:

minor allele frequency

ORs:

odds ratios

SNPs:

single nucleotide polymorphisms

TC:

total cholesterol

TG:

triglyceride

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Acknowledgments

This study was supported by research funds from the National Natural Science Foundation (30525031 and 30430590) and the National Key Basic Research and Development Program (2002CB512905) of China. Dr. Frank B. Hu’s work was supported in part by the American Heart Association Established Investigator Award.

We are particularly grateful to all individuals who participated in the present study and to the medical personnel of Tongji Hospital, Union Hospital, and Wugang Hospital in Wuhan city, Hubei Province, China.

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Correspondence to Frank B. Hu or Tangchun Wu.

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The first two authors contributed equally to this paper.

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He, MA., Zhang, X., Wang, J. et al. Genetic variation in heat shock protein 60 gene and coronary heart disease in China: tagging-SNP haplotype analysis in a case-control study. Cell Stress and Chaperones 13, 231–238 (2008). https://doi.org/10.1007/s12192-008-0025-5

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  • DOI: https://doi.org/10.1007/s12192-008-0025-5

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