Systematic sequencing of the coding and exon flanking regions of the apolipoprotein (apo) A-I gene has identified a new polymorphic Msp I site (C C/T-GG). This polymorphism is situated between the transcriptional starting site and the signal peptide start coding site (intron 1), so may influence the efficiency of surrounding splicing, thereby interfering with the expression of the apo A-I gene product, or serve as a linkage marker with a hitherto unidentified mutation defect responsible for hyperlipidemia and/or premature coronary heart disease. However, there was no significant difference in the allele frequencies between control and coronary heart disease subjects in a Japanese population. The -78 G-->A promoter polymorphism of apo A-I, previously reported in Western populations, has also been analyzed. The results show that neither mutation is likely to be the etiology for predisposition to a change of high-density lipoprotein cholesterol and/or variation in lipid and lipoprotein levels, or for the occurrence of coronary heart disease in Japanese populations.