A promoter variant of the ATP-binding cassette transporter A1 gene alters the HDL cholesterol level in the general Japanese population

To investigate the effects of polymorphisms in the ATP-binding cassette transporter A1 ( ABCA1 ) gene on the high-density lipoprotein cholesterol (HDL-C) level and the incidence of myocardial infarction (MI), we performed association studies. Sequence analysis identified 14 polymorphisms in the promoter region of ABCA1 . After considering linkage disequilibrium, three polymorphisms in the promoter region and 11 polymorphisms from the JSNP database were determined in 1,880 subjects recruited from the Suita Study, representing the general population in Japan. We evaluated the association between the ABCA1 genotype and HDL-C level adjusted not only for standard factors, but also for genetic factors including ApoA1 and ApoE genotypes. Of the 14 polymorphisms tested, the G(−273)C ( P =0.0074), C(−297)T ( P =0.0195), and IMS-JST071749 ( P =0.0093) polymorphisms were significantly associated with the HDL-C level in the Suita population. We could reconfirm that the G(−273)C genotype was influential in another set of subjects ( P =0.0310, n =743). However, the distribution of the ABCA1 G(−273)C genotype in subjects with MI ( n =598) was not different from that in the control population ( n =801). These results indicate that ABCA1 G(−273)C has a significant effect on the HDL-C level in the general Japanese population, but not on the incidence of MI.