ANALYSIS OF THE ASSOCIATION OF A HEAT-SHOCK PROTEIN70-1 GENE PROMOTERPOLYMORPHISM WITH MYOCARDIAL-INFARCTION AND CORONARY RISK TRAITS

Heat shock proteins (HSP) are induced during coronary ischaemia, and a bnormal expression of one HSP gene may cause hypertension in rats. We examined association of a promoter polymorphism in the major stress-in ducible hsp70 gene (hsp70-1 or HSP70A1) on chromosome 6 (p21.3) with c oronary disease traits. This C-->A base substitution (AAA (C) under ba r CCC) is at nucleotide position-110 in the heat shock transcription f actor 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 age-matched controls. The f requency 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/m(2) +/-3.9) compa red with homozygotes for the common C-110 allele (26.3 kg/m(2) +/-3.3) . The rarer homozygotes were shorter and heavier than the common homoz ygotes. A follow-up study involved 1431 healthy, middle aged men from the UK (NPHSII group). The frequency of the A(-100) 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.