RFLP Markers of Familial Coronary Heart Disease

Abstract

In two population samples of men aged 30–59 years from the North of Edinburgh, a higher frequency of CHD in those with a family history of the disease in close relatives before age 60 was strongly associated with the allele status of four RFLP in the apo AI/CIII/AIV gene region. In a simultaneous multiple logistic regression analysis of CHD on a number of covariates, a family history emerged with significant odds ratio of 2.553 (p = 0.034) in subjects with minor RFLP alleles in one of the samples and with odds ratio of 3.611 (p = 0.016) in those homozygous for major alleles in the other. The apo AI/CIII/AIV related effect of family history on evidence of CHD was independent of all other variables tested, which included age, cigarette smoking, hypertension, hyperlipldaemia, socio-economic group and obesity. There was no evidence of a familial environment effect or of genotype environment interaction. The results of these studies suggest that genetic liability to CHD is influenced significantly by a locus or loci in the apo AI/CIII/AIV gene region. Since the association of this region with familial CHD involves different alleles or haplotypes in different sections of the population (different linkage phase) no single allele or haplotype identifies an individual with increased liability to CHD on account of this association. This may explain the apparently conflictng results obtained in case control studies.