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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.

Because of its variations in length, the AT rich Hyper-Variable Region (HVR) of the 3' end of the Apolipoprotein B gene is used as a polymorphic maker in genetic studies. It contains a SspI site in its repeated motif and we used this feature to precisely analyse the internal structure of the different alleles found at this locus in a Caucasian population. We performed total digestion on 194 alleles as well as Minisatellite Variant Repeat mapping (MVR mapping: partial digestion) on 54. The results show that the level of length variability (in copy number) of the 5' end of this locus is at least two times higher than that of the 3' end. This could be correlated with the difference in nucleotide sequence between the two parts of the HVR and suggests the dependence on the primary structure of the mechanism that produces length variability. A molecular model is proposed to explain this result. Moreover, the sharp analysis of the minisatellite structure by the distribution of SspI sites reveals differences between long and short alleles, indicating that in most cases, no recombination occurs between alleles of different sizes. Finally the rare alleles exhibit a non-canonical structure. These important points could explain the bimodal distribution of the frequencies of the alleles in the population.

In a European study an insertion (/)/deletion (D) polymorphism in the angiotensin converting enzyme (ACE) gene has been shown to be associated with the risk of myocardial infarction (Ml). In the same study, we investigated the association of the polymorphism with a parental history of fatal MI. There was an excess of both DD (odds ratio 2·6, p=0·02) and ID (odds ratio=1·9, p=0·08) genotypes among those having a parental history of Ml, confirming that genetic variation in the ACE locus could be involved in the risk of MI.

Human apolipoprotein (apo) E, a polymorphic protein with three common alleles, epsilon 2, epsilon 3, and epsilon 4, plays an important role in lipoprotein metabolism. This article describes the association of this polymorphism with lipids, apolipoproteins, and lipoproteins with a particular regard to lipoprotein particles, as defined by their apolipoprotein content, as well as the risk of myocardial infarction in a multicenter population-based case-control study (ECTIM study). In the ECTIM study, 574 male patients aged 25 to 64 were examined 3 to 9 months after myocardial infarction in four regions participating in the World Health Organization MONICA project: Belfast (Northern Ireland) and Lille, Strasbourg, and Toulouse (France). Control subjects (n = 722) were randomly selected from the regional populations. The distribution of apoE phenotypes was significantly different across the four control samples (P = .04), with a higher frequency of the epsilon 4 allele in Belfast (14.3%) than in Toulouse (8.2%). The association of apoE polymorphism with biological measurements was studied in the control groups (n = 640) after men with coronary heart disease or those taking hypolipidemic drugs were omitted, with the apoE3/3 phenotype as a reference after adjustment for concomitant factors. Individuals carrying the epsilon 2 allele had lower levels of plasma cholesterol, low-density lipoprotein cholesterol (LDL-C), and apoB and higher levels of triglycerides, very-low-density lipoprotein cholesterol (VLDL-C), apoC-III, apoE, lipoprotein (Lp) C-III:B, and Lp E:B. However, the effect of the epsilon 2 allele on triglyceride, VLDL-C, apoE, and Lp E:B parameters was heterogeneous across the populations.(ABSTRACT TRUNCATED AT 250 WORDS)