Analysis of the association of a heat shock protein70-1 gene promoter polymorphism with myocardial infarction and coronary risk traits.

M.K Bolla,D Arveiler,D.S Latchman,J.P Cambou,D.M Yellon,S.E Humphries,I.N.M Day,G.J Miller,A Evans,G Luc,F Cambien

doi:10.1155/1998/235151

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 centers in France, consisted of 578 myocardial infarction cases and 698 age-matched controls. The frequency of the A-110 allele 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-110 allele had a higher BMI (27.3 kg/m2 +/- 3.9) compared with homozygotes for the common C-110 allele (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 (NPHS II group). The frequency of the A-110 allele 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.

Highlights

The heat shock response was originally discovered by Ritossa (1962) in Drosophila busckii, in response to heat, and, subsequently is was shown (Tissieres et aI., 1974) thatM .K
Tel.: +441712096962, Fax: +441712096212; Email: rmhaseh@ucl.ac,uk the appearance of chromosome puffs coincided with the synthesis of a small number of proteins, the heat shock proteins
Heat shock proteins are known to be induced by a diverse array of cellular stresses other than elevated temperature, including those that are encountered during myocardial ischaemia

Summary

Introduction

The heat shock response was originally discovered by Ritossa (1962) in Drosophila busckii, in response to heat, and, subsequently is was shown (Tissieres et aI., 1974) thatM .K. Heat shock proteins are known to be induced by a diverse array of cellular stresses other than elevated temperature, including those that are encountered during myocardial ischaemia. The function of this response has not been determined. The transcriptional control of hsp is complex and the 5' tlanking region of the gene contains binding sites for a number of transcription factors, including TFIlD, AP2, ATF, and Sp I, as well as CCAAT and purine-rich box motifs. Upon exposure to stressful stimuli , oligomerization of proteins called heat shock factors (HSF) occurs and , binding to the HSE in the promoter, initiates transcription of the gene. Located five bases upstream of the first of these motifs is a C---7A polymorphism (Cascino et al, 1993) at nucleotide position -110 (Fig. J)

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Conclusion