DNA polymorphisms at the apolipoprotein A1-CIII loci in Taiwanese: Correlation of plasma apoCIII with triglyceride level and body mass index

Background and purpose: Apolipoprotein (APO) A1-CIII genes are linked withi n a 2.6-kb region on human chromosome 11. ApoA1 is the main component of hi gh-density lipoprotein (HDL), and apoCIII inhibits lipoprotein lipase activ ity. Genetic variations in APOA1-CIII may affect the function of apoA1/apoC III and plasma lipid/lipoprotein levels, and thus, the risk of developing a therosclerosis. This study compared the frequency distributions of genetic variations in APOA1-CIII genes and their influence on plasma lipid concentr ations in Taiwanese patients with coronary artery disease (CAD) and in heal thy controls. Methods: Six restriction site variations (RSVs) of the APOA1-CIII gene comp lex were investigated by DNA amplification using polymerase chain reaction and restriction enzyme digestion in 229 control subjects and 131 CAD patien ts during the period from 1992 through 1996. The blood lipid profiles of th ese subjects were also determined. Results: Thirty-seven distinct sh-RSV genotypes were observed. Separate com parisons of the frequency distributions of the six genetic variations showe d no significant differences between CAD patients and controls subjects, bu t the combined six-RSV-genotypes showed different frequency distributions b etween these two groups. Nine of the 31 six-RSV genotypes were found only i n the CAD patients and higher frequencies of two of these types were observ ed in the CAD patients than in healthy controls. The effects of these genet ic variations were on high-density lipoprotein cholesterol in women (for Ms pIB, PstI, SstI and PvuII RSV) and total cholesterol (for PvuII RSV), low-d ensity lipoprotein cholesterol (for XmnI RSV), and apolipoprotein B (for Ms pI and SstI RSV) levels in men in the control group. Elevated plasma apoCII I concentration was significantly associated dth an increased plasma trigly ceride level and body mass index in the control group (P < 0.0001). Conclusions: Analysis of the frequency distribution of six RSVs of the APOA 1-CIII gene complex in Taiwanese CAD patients and control subjects showed t hat the effect of genotype on plasma lipid levels was gender-specific and t hat the apoCIII level was closely associated with plasma triglyceride level and body mass index.