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APO C-III ABSTRACTS: DNA restriction fragment length polymorphisms as markers of familial coronary heart disease.

Price WH, Morris SW, Kitchin AH, Wenham PR, Burgon PR, Donald PM University Department of Medicine, Western General Hospital, Edinburgh. [Lancet 1989 Jun 24;1(8652):1407-11]

246 of 713 men aged 30 to 59 years had first-degree relatives who had had coronary heart disease (CHD) by the age of 60; men with a family history of CHD were twice as likely to have CHD themselves, compared with those without such a family history. At least 75% of the difference was accounted for by CHD in men with minor alleles of 4 restriction fragment length polymorphisms (RFLPs) in the region of the apolipoprotein (apo) AI and apo CIII genes. The RFLPs were identified with the restriction enzymes XmnI, PstI, MspI, and SacI. Each polymorphism has two alleles (major and minor), designated X1 and X2, P1 and P2, M1 and M2, and S1 and S2, respectively. In men with any one of the minor alleles, a family history of CHD was associated with a 234% increase in CHD prevalence. In men with major alleles only, a family history of CHD was not associated with any significant increase in CHD. The effect of the minor alleles was not significantly altered when plasma lipids and other variables except for age were taken into account. The association between the minor RFLP alleles and polymorphic gene variants (probably the apo AI, apo CIII, or both genes) which enhance liability to CHD accounted for almost 20% of total CHD in this population.

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