Prevalence and associations of apolipoprotein A-I linked DNA polymorphisms: results from a population study

Subjects from a geographically defined population were screened for restriction fragment length polymorphisms linked to the apolipoprotein A-I (apoaA-I) gene locus. The polymorphic DNA fragments detected with an apoA-I cDNA probe after digestion with the restriction endonucleases Sac I (S1 and S2 alleles), Msp I (M1 and M2 alleles), or Pst I (P1 and P2 alleles) were used to define polymorphic haplotypes. The uncommon S2M1 haplotype was present in the leukocyte genomic DNAs of 6 of 22 (27%) subjects with high-density lipoprotein cholesterol (HDL-C) levels in the lowest decile, in contrast to none of the 20 subjects with HDL-C levels in the highest decile. With repeat determinations of the HDL-C levels 10 years later, the levels of the subjects in the low decile group with the S1M1 haplotype had regressed toward the population mean, while the regression was much less substantial for the S2M1 group. The mean triglyceride (TG) level in low HDL-C subjects with the S2M1 haplotype was also higher than in those without it (295 vs 246 mg/dl), although not all of those with the S2M1 pattern were hypertriglyceridemic. The prevalence of the P2 allele was increased in a series of men with angiographically confirmed premature coronary artery disease (CAD) (P2 present in 7 of 43) as compared to a group of age-matched controls without CAD (1 of 36). There was no difference between these groups in the prevalence of the S2 allele. These results suggest that a particular pattern of apoA-I linked genetic polymorphisms is associated with lower HDL-C levels. This type of analysis will be useful in studies of the epidemiology of abnormal lipid states and may eventually provide a genetic marker to identify those at risk can be effectively instituted.