title: Functional SNPs in HSPA1A gene predict risk of coronary heart disease.
abstract: BACKGROUND
  HSP70 plays crucial roles in endothelial cell apoptosis, which is involved in the early phase and progress of coronary heart disease (CHD). However, the association between polymorphisms of HSP70 genes and the risk of CHD still remains unclear. Our aim was to determine whether genetic variants in the HSPA1A gene are associated with the risk of CHD.
  
  
  RESULTS
  By resequencing and genotyping, the associations of 2 single nucleotide polymorphisms (SNPs) +190G/C (rs1043618) and -110A/C (rs1008438) in the HSPA1A gene with risk of CHD were determined in a 1,003 pairs case-control study. The SNP function was further analyzed using a luciferase reporter assay in two cell lines. The results indicated that +190CC genotype was associated with significantly higher risk of CHD when compared with +190GG genotype (OR = 1.56, 95% CI: 1.10-2.20, P = 0.012), while association between -110A/C polymorphism and CHD was not statistically significant (P>0.05). However, the -110C/+190C haplotype had a significantly higher risk of CHD when compared with the -110A/+190G haplotype (OR = 1.17, 95% CI: 1.01-1.34, P = 0.031). Luciferase reporter assays showed that the +190C allele resulted in 14% ~ 45% reduction in luciferase expression in endothelial and non-endothelial cells when compared with the +190G allele.
  
  
  CONCLUSIONS
  The identified genetic variants in the HSPA1A gene combinatorially contribute towards the susceptibility to CHD likely by affecting the level of synthesis of HSP70. This study may provide useful markers for identification of subjects at risk for CHD.
authors.affiliation: 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.
authors.forename: Meian
authors.initials: M
authors.lastname: He
authors.forename: Huan
authors.initials: H
authors.lastname: Guo
authors.forename: Xiaobo
authors.initials: X
authors.lastname: Yang
authors.forename: Xiaomin
authors.initials: X
authors.lastname: Zhang
authors.forename: Li
authors.initials: L
authors.lastname: Zhou
authors.forename: Longxian
authors.initials: L
authors.lastname: Cheng
authors.forename: Hesong
authors.initials: H
authors.lastname: Zeng
authors.forename: Frank B
authors.initials: FB
authors.lastname: Hu
authors.forename: Robert M
authors.initials: RM
authors.lastname: Tanguay
authors.forename: Tangchun
authors.initials: T
authors.lastname: Wu