Henkhaus Rebecca S, Dodani Sunita, Manzardo Ann M, Butler Merlin G
University of Kansas Medical Center, Departments of Psychiatry and Behavioral Sciences and Pediatrics, USA.
Indian J Hum Genet. 2011 Sep;17(3):194-200. doi: 10.4103/0971-6866.92103.
Coronary artery disease (CAD) is a leading cause of death in the United States. South Asian immigrants (SAIs) from the Indian subcontinent living in the US are disproportionately at higher risk of CAD than other immigrant populations. Unique genetic factors may predispose SAIs to increased risk of developing CAD when adopting a Western lifestyle including a higher-fat diet, more sedentary behavior and additional gene-environment interactions. SAIs are known to have low levels of the protective high density lipoprotein (HDL) and an altered function for Apo-lipoprotein A-1 (ApoA1), the main protein component of HDL cholesterol. One gene that may be genetically distinctive in this population is APOA1 which codes for ApoA-1 protein, a potentially important contributing factor in the development of CAD.
DNA sequencing was performed to determine the status of the seven single-nucleotide polymorphisms (SNPs) in the APOA1 gene from 94 unrelated SAI adults. Genotypes, allelic frequencies, and intragenic linkage disequilibrium of the APOA1 SNPs were calculated.
Several polymorphisms and patterns were common among persons of south Asian ethnicity. Frequencies for SNPs T655C, T756C and T1001C were found to be different than those reported in European Caucasian individuals. Linkage disequilibrium was found to be present between most (13 of 15) SNP pairings indicating common inheritance patterns.
SAIs showed variability in the sequence of the APOA1 gene and linkage disequilibrium for most SNPS. This pattern of APOA1 SNPs may contribute to decreased levels of HDL cholesterol reported in SAIs, leading to an increased risk for developing CAD in this population.
冠状动脉疾病（CAD）是美国主要的死亡原因。生活在美国的来自印度次大陆的南亚移民（SAIs）患CAD的风险比其他移民群体高得多。当采用西方生活方式，包括高脂肪饮食、久坐行为以及额外的基因 - 环境相互作用时，独特的遗传因素可能使SAIs患CAD的风险增加。已知SAIs的保护性高密度脂蛋白（HDL）水平较低，且载脂蛋白A - 1（ApoA1）功能改变，ApoA1是HDL胆固醇的主要蛋白质成分。在该人群中可能具有遗传独特性的一个基因是APOA1，它编码ApoA - 1蛋白，这是CAD发展中一个潜在的重要促成因素。
对94名无关的SAI成年个体的APOA1基因中的7个单核苷酸多态性（SNP）进行DNA测序，计算APOA1 SNP的基因型、等位基因频率和基因内连锁不平衡。
几种多态性和模式在南亚种族人群中很常见。发现SNP T655C、T756C和T1001C的频率与欧洲白种人个体中报道的频率不同。在大多数（15对中的13对）SNP配对之间发现存在连锁不平衡，表明存在共同的遗传模式。
SAIs在APOA1基因序列和大多数SNP的连锁不平衡方面表现出变异性。这种APOA1 SNP模式可能导致SAIs中HDL胆固醇水平降低，从而增加该人群患CAD的风险。
