Analysis of the Association of A Heat Shock Protein70-1 Gene Promoter Polymorphism With Myocardial Infarction and Coronary Risk Traits

Author:

Bolla M.K.1,Miller G.J.2,Yellon D.M.3,Evans A.4,Luc G.5,Cambou J.P.6,Arveiler D.7,Cambien F.8,Latchman D.S.9,Humphries S.E.1,Day I.N.M.1

Affiliation:

1. Cardiovascular Genetics, Department of Medicine, University College London Medical School, The Rayne Institute, 5 University Street, London WCIE 6JJ, UK

2. MRC Epidemiology and Medical Care Unit, Wolfson Institute of Prevelllive Medicine, The Medical College of ST. Bartholomew's Hospital, Charterhouse Square, London EC1M 6BQ, UK

3. Division of Cardiology, Hatter Institute for Cardiovascular Studies, University College Hospital, Grafton Way, London WC1, UK

4. MONICA project, Belfast, UK

5. MONICA project, Lille, France

6. MONICA project, Toulouse, France

7. MONICA project, Strasbourg, France

8. INSERM, SC7-17, rue du Fer à Moulin, 75005 Paris, France

9. Department of Molecular Pathology, Windeyer Building, Cleveland Street, London WCIP 6DB, UK

Abstract

Heat shock proteins (HSP) are induced during coronary ischaemia, and abnormal expression of one HSP gene may cause hypertension in rats, We examined association of a promoter polymorphism in the major stress-inducible hsp70 gene (hsp70-1 or HSP70A1) on chromosome 6 (p21.3) with coronary disease traits, This C→A base substitution (AAACCCC) is at nucleotide position -110 in the heat shock transcription factor binding site (heat shock element, HSE). The first study sample (ECTIM), recruited from Belfast and three centres in France, consisted of 578 myocardial infarction cases and 698 agematched controls. The frequency of the A-110allele was 0.381 (95% CI=0.35-0.41) and 0.384 (95% CI=0.36-0.41) in cases and controls respectively, Homozygotes for the rarer A-110allele had a higher BMI (27.3 kg/m2±3.9) compared with homozygotes for the common C-110allele (26.3 kg/m2±3.3), The rarer homozygotes were shorter and heavier than the common homozygotes. A follow-up study involved 1431 healthy, middle aged men from the UK (NPHSII group). The frequency of the A-110allele was 0.385 (95% CI=0.37 -0.40), and there was no association of genotype with BMI. Thus there appears to be no strong association of the Hsp70-1 promoter polymorphism with risk of myocardial infarction, BMI or any coronary disease traits analysed here.

Publisher

Hindawi Limited

Subject

Biochemistry (medical),Clinical Biochemistry,Genetics,Molecular Biology,General Medicine

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