Functional SNPs in HSPA1A Gene Predict Risk of Coronary Heart Disease

• Published in: PloS one Vol. 4; no. 3; p. e4851
• Main Authors: He, Meian, Guo, Huan, Yang, Xiaobo, Zhang, Xiaomin, Zhou, Li, Cheng, Longxian, Zeng, Hesong, Hu, Frank B., Tanguay, Robert M., Wu, Tangchun
• Format: Journal Article
• Language: English
• Published: United States Public Library of Science 31.03.2009; Public Library of Science (PLoS)
• Subjects: Alleles; Apoptosis; Cardiology; Cardiovascular disease; Cardiovascular diseases; Cardiovascular Disorders/Coronary Artery Disease; Case-Control Studies; Cell lines; Coronary artery disease; Coronary Disease - genetics; Coronary heart disease; Development and progression; Disease susceptibility; Education; Endothelial cells; Endothelium; Genes; Genetic aspects; Genetic diversity; Genetic Predisposition to Disease; Genetic variance; Genetics and Genomics/Functional Genomics; Genomes; Genotype; Genotyping; Haplotypes; Health risks; Heart attacks; Heart diseases; Heat shock proteins; Hospitals; HSP70 Heat-Shock Proteins - genetics; Hsp70 protein; Humans; Luciferase; Medical research; Medicine; Parkinson's disease; Polymorphism; Polymorphism, Single Nucleotide - physiology; Public health; Public Health and Epidemiology; Risk; Risk factors; Science; Single nucleotide polymorphisms; Single-nucleotide polymorphism; Statistical analysis; China
• ISSN: 1932-6203; 1932-6203
• DOI: 10.1371/journal.pone.0004851

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. 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. 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.