MspI polymorphism at+83 bp in intron 1 of the human apolipoprotein A1 geneis associated with elevated levels of HDL cholesterol and apolipoprotein A1 in nondiabetic subjects but not in type 2 diabetic patients with coronaryheart disease

OBJECTIVE - Elevated HDL cholesterol and its principal carrier protein apol ipoprotein Al [apo(al)] are associated with reduced risk of coronary heart disease (CHD). No studies are available on the impact of the -75-bp and/or +83-bp polymorphisms of the apo(al) gene on HDL cholesterol and apo(al) lev els in patients with type 2 diabetes. RESEARCH DESIGN AND METHODS - We determined the prevalence of the - 75-bp a nd +83-bp polymorphisms of the apo(al) gene by restriction fragment length polymorphism analysis among 308 unrelated nondiabetic subjects with CHD and among 251 unrelated patients with type 2 diabetes with CHD and in randomly selected 82 healthy men (CHD-). RESULTS - The rare M1(-) and M2(-) allele frequencies of the apo(al) gene w ere 23 and 1.8%, respectively among control subjects, 20 and 1.5%, respecti vely, among nondiabetic subjects with CHD, and 22 and 2.6%, respectively, a mong patients with type 2 diabetes and CHD (NS). Nonsmoking nondiabetic sub jects with CHD having the M2(+-) genotype had higher HDL cholesterol (1.48 +/- 0.19 vs. 1.23 +/- 0.02 mmol/l, P < 0.01) and apo(al) (1.43 +/- 0.10 vs. 1.36 +/- 0.02 g/l, P < 0.05) levels than subjects with the M2++ genotype, even after adjustment for confounding factors. This association was not fou nd among patients with type 2 diabetes and CHD. CONCLUSIONS - We conclude that the +83-bp polymorphism of the apo(al) gene is associated with elevated HDL cholesterol and apo(al) levels in Finnish n ondiabetic subjects but not in patients with type 2 diabetes.