SEQUENCE VARIATION IN THE APOA2 GENE AND ITS RELATIONSHIP WITH PLASMA HDL-CHOLESTEROL LEVELS

摘要: Coronary heart disease (CHD) is a major public health concern, affecting almost 16 million people in the U.S. and leading to 452,300 deaths 2004 alone. Low levels of high density lipoprotein (HDL) cholesterol have been shown increase risk for cardiovascular (CVD). The role genetics total cholesterol, HDL-cholesterol, triglycerides significant, with heritability estimates exceeding 50%. Recent studies identified loci associated HDL-cholesterol through genome-wide association studies, which investigated influences common variants on traits. Relatively few impact rare (or modest affect) disease. aim our study was evaluate genetic variation APOA2 (a biological candidate gene involved HDL metabolism) relation epidemiological samples African Blacks Non-Hispanic Whites (NHWs). We resequenced individuals upper 5th percentile (47 NHWs 48 Blacks) lower (48 47 Blacks), allowing us identify both variants. Common tagSNPs all screened larger NHW Black associations levels. detected 26 (25 single nucleotide substitutions 1 microsatellite); 12 were previously unreported. Of new variants, 6 present Blacks. observed an increased number minor alleles (either heterozygosity or homozygosity variants) subjects low levels, more pronounced NHWs. performed preliminary analysis using 9 that (n=624, 8 (n=788, 5 TaqMan SNP genotyping assays date. For NHWs, we found significant only females 2233C>T/rs6413453 (p=0.028) 3251A>G (p=0.023). Completing remaining will allow determine extent influence