Functional SNPs in HSPA1A Gene Predict Risk of Coronary Heart Disease 英文参考文献.docVIP

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Functional SNPs in HSPA1A Gene Predict Risk of Coronary Heart Disease 英文参考文献.doc

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Functional SNPs in HSPA1A Gene Predict Risk of Coronary Heart Disease 英文参考文献

FunctionalSNPsinHSPA1AGenePredictRiskof CoronaryHeartDisease MeianHe1,2.,HuanGuo1.,XiaoboYang1,XiaominZhang1,LiZhou1,LongxianCheng2,HesongZeng3, FrankB.Hu4,RobertM.Tanguay5,TangchunWu1* 1Institute of Occupational Medicine and the Ministry of Education Key Lab of Environment and Health, School of Public Health, Tongji Medical College, Huazhong UniversityofScienceandTechnology,Wuhan,Hubei,China,2DepartmentofCardiology,UnionHospital,TongjiMedicalCollege,HuazhongUniversityofScienceand Technology,Wuhan,Hubei,China,3DepartmentofCardiology,TongjiHospital,TongjiMedicalCollege,HuazhongUniversityofScienceandTechnology,Wuhan,Hubei, China, 4Departments of Nutrition and Epidemiology, Harvard School of Public Health, Boston, Massachusetts, United States of America, 5Laboratory of Cellular and DevelopmentalGenetics,DepartmentofMedicine,FacultyofMedicine,andCREFSIP,PavilionC.E.Marchand,Universite′ Laval,Que′bec, Canada Abstract Background:HSP70playscrucialrolesinendothelialcellapoptosis,whichisinvolvedintheearlyphaseandprogressof coronaryheartdisease(CHD).However,theassociationbetweenpolymorphismsofHSP70genesandtheriskofCHDstill remainsunclear.OuraimwastodeterminewhethergeneticvariantsintheHSPA1Ageneareassociatedwiththeriskof CHD. Methodology/PrincipalFindings:Byresequencingandgenotyping,theassociationsof2singlenucleotidepolymorphisms (SNPs)+190G/C(rs1043618)and2110A/C(rs1008438)intheHSPA1AgenewithriskofCHDweredeterminedina1,003 pairscase-controlstudy.TheSNPfunctionwasfurtheranalyzedusingaluciferasereporterassayintwocelllines.Theresults 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),whileassociation between2110A/C polymorphism andCHD wasnot statistically significant (P.0.05). However, the 2110C/+190C haplotype had a significantly higher risk of CHD when compared with the 2110A/+190G haplotype (OR=1.17, 95% CI: 1.01–1.34, P=0.031). Luciferase reporter assays showed