Association of ATP binding cassette transport-A1 gene R219K polymorphism in male with Ischemic Cerebrovascular Disease

• Main Authors: Yen-Ling Chen, 陳妍伶
• Other Authors: Shyi-Jang Shin
• Format: Others
• Language: zh-TW
• Published: 2006
• Online Access: http://ndltd.ncl.edu.tw/handle/09939720707381766803

碩士 === 高雄醫學大學 === 醫學研究所碩士班 === 94 === Background The membrane transporter Adenosine triphosphate-binding cassette transporter A1 (ABCA1) is transmembrane protein with two membrane domains and two ATP subunits. The ABC proteins bind ATP and use the energy to drive the transport of various molecules across the membranes. ABCA1 is believed involved in mediating cholesterol and phospholipid efflux from peripheral cells to Apolipoprotein A-I, and was known to play a key role in lipid homeostasis and atherosclerosis. Mutations within the ABCA1 gene are associated with decreased HDL-C, increased triglycerides, and slowly to cholesterol efflux from peripheral cells, that is an increased risk of CHD.The R219K variant of the ABCA1gene has been associated decreased triglycerides and a trend to increased HDL, and reduced severity of atherosclerosis, fewer coronary events, and protective to progression atherosclerosis in CHD. However, the risk association between ABCA1 R219K polymorphism and ischemic cerebrovascular disease (CVD) had never been reported. Thus, we hypothesized that genetic common variability in ABCA1 may influence cholesterol metabolism in the vascular atherosclerosis and interfere with the development of CVD. Methods and Material ABCA1 R219K genotypes were determined by PCR-RFLP, in a group of 374 subjects with CVD and 403 CVD disease-free controls (aged 65 to 80 years). Statistical analysis All data are reported as the mean ± SD. The differences in genotypes distribution and allele frequences between stroke and control subject were analysed by student’ t test and logistic regression. Statistical significance was assumed at P<0.05. Results The R219K variant has a carrier frequency of 43.8% in Taiwanese. The distribution of R219K genotype variant was not statistically different between CVD subjects and controls. While the R219K variant was significantly lower in men of CVD subjects than that of control male. The odds ratio in men with K variant in patients with CVD subjects when compared with controls was highly statistical significant (OR=2.62, 95% CI=1.03~7.04, P<0.05), suggests that in men have the R allele of the R219K variant have a higher CVD risk. When CVD subjects was smoking in men, there has no increment in CVD risk in the R allele of the R219K variant.We found the of R219K genotype variant was not statistically different in the plasma of Interleukin-1 βeta concentration between CVD subjects and controls. Conclusions These data suggest that male with the R219K variant of ABCA1 gene had decreased risk of development of ischemic CVD independent of lipid level.