RGD Reference Report - Functional SNPs in HSPA1A gene predict risk of coronary heart disease. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Functional SNPs in HSPA1A gene predict risk of coronary heart disease.

Authors: He, M  Guo, H  Yang, X  Zhang, X  Zhou, L  Cheng, L  Zeng, H  Hu, FB  Tanguay, RM  Wu, T 
Citation: He M, etal., PLoS One. 2009;4(3):e4851. doi: 10.1371/journal.pone.0004851. Epub 2009 Mar 31.
RGD ID: 7257652
Pubmed: PMID:19333379   (View Abstract at PubMed)
PMCID: PMC2659421   (View Article at PubMed Central)
DOI: DOI:10.1371/journal.pone.0004851   (Journal Full-text)

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. METHODOLOGY/PRINCIPAL FINDINGS: 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/SIGNIFICANCE: 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.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
Coronary Disease  IAGP 7257652DNA:SNPs: : -110A>C (rs1008438), 190G>C (rs1043618) (human)RGD 
Coronary Disease  ISOHSPA1A (Homo sapiens)7257652; 7257652DNA:SNPs: : -110A>C (rs1008438), 190G>C (rs1043618) (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Hspa1a  (heat shock protein family A (Hsp70) member 1A)

Genes (Mus musculus)
Hspa1a  (heat shock protein 1A)

Genes (Homo sapiens)
HSPA1A  (heat shock protein family A (Hsp70) member 1A)


Additional Information