Saleheen Danish, Khanum Shaheen, Haider Shajjia R, Nazir Aisha, Ahmad Usman, Khalid Hamza, Hussain Imad, Shuja Fahad, Shahid Kamran, Habib Aisha, Frossard Philippe M
Department of Biological and Biomedical Sciences, Medical College, Aga Khan University, Stadium Road, Karachi-74800, Pakistan.
Int J Cardiol. 2007 Jan 31;115(1):7-13. doi: 10.1016/j.ijcard.2005.12.020. Epub 2006 Jun 23.
ATP-binding cassette transporter 1 (ABCA1) is a trans-membrane protein responsible for the efflux of cholesterol and phospholipids across the cell membrane, an essential step in the reverse cholesterol transport system. This study investigates the effect of five non-synonymous SNPs of ABCA1 gene on plasma HDL-C levels in Pakistani individuals free of ischemic heart disease and stroke.
Five non-synonymous SNPs were selected after sequencing ABCA1 gene in patients of Hypoalphalipoproteinemia. The presence of these SNPs was then checked in 200 individuals by using PCR-RFLP. Plasma glucose and lipid fractions were measured in fasting state. Ethical approval was obtained from the Ethical Review Committee, Aga Khan University and informed consent was obtained from all subjects.
LL genotype of V825L polymorphism was associated with decreased levels of HDL-C [-0.17 (-0.32 to -0.19); P=0.02] and P774 allele showed a significant increase in HDL-C levels as compared to T774 allele [-0.15 (-0.18 to -0.02); P=0.01]. R219K, A399V and V771M polymorphisms did not show any association with levels of HDL-C, LDL-C, cholesterol and triglycerides. Haplotype analysis between R219K and V825L polymorphisms showed a unique interaction between R219 allele and L825 allele. The RL haplotype was found to be associated with decreased levels of HDL-C [-0.12 (-0.22 to -0.03); P=0.001].
ABCA1 polymorphisms are associated with varying levels of HDL-C in Pakistani individuals. These results warrant further investigations as ABCA1 polymorphisms may have a major role in the high incidence of cardiovascular disorders in South Asians.
ATP结合盒转运蛋白1（ABCA1）是一种跨膜蛋白，负责胆固醇和磷脂跨细胞膜的外流，这是逆向胆固醇转运系统中的关键步骤。本研究调查了ABCA1基因的五个非同义单核苷酸多态性（SNP）对无缺血性心脏病和中风的巴基斯坦个体血浆高密度脂蛋白胆固醇（HDL-C）水平的影响。
在低α脂蛋白血症患者中对ABCA1基因进行测序后选择了五个非同义SNP。然后通过聚合酶链反应-限制性片段长度多态性（PCR-RFLP）在200名个体中检测这些SNP的存在。在空腹状态下测量血浆葡萄糖和脂质成分。获得了阿迦汗大学伦理审查委员会的伦理批准，并获得了所有受试者的知情同意。
V825L多态性的LL基因型与HDL-C水平降低相关[-0.17（-0.32至-0.19）；P=0.02]，与T774等位基因相比，P774等位基因显示HDL-C水平显著升高[-0.15（-0.18至-0.02）；P=0.01]。R219K、A399V和V771M多态性与HDL-C、低密度脂蛋白胆固醇（LDL-C）、胆固醇和甘油三酯水平均无关联。R219K和V825L多态性之间的单倍型分析显示R219等位基因和L825等位基因之间存在独特的相互作用。发现RL单倍型与HDL-C水平降低相关[-0.12（-0.22至-0.03）；P=0.001]。
ABCA1多态性与巴基斯坦个体中不同水平的HDL-C相关。由于ABCA1多态性可能在南亚人心血管疾病的高发病率中起主要作用，这些结果值得进一步研究。
