Novel polymorphisms in promoter region of ATP binding cassette transporter gene and plasma lipids, severity, progression, and regression of coronary atherosclerosis and response to therapy
Novel polymorphisms in promoter region of ATP binding cassette transporter gene and plasma lipids, severity, progression, and regression of coronary atherosclerosis and response to therapy
复制标题
DOI：
10.1161/hh0901.090301
复制
发表时间：
2001-05-11
影响因子：
20.1
通讯作者：
Marian, AJ
中科院分区：
文献类型：
--
作者：
Lutucuta, S;Ballantyne, CM;Marian, AJ
丹吉尔病患者的 ATP 结合盒转运蛋白 (ABCA1) 基因突变，这些患者表现出高密度脂蛋白胆固醇 (HDL-C) 和载脂蛋白 A1 (apoA1) 水平降低以及过早冠状动脉粥样硬化，因此我们得出这样的假设：ABCA1 基因中的常见多态性可以决定普通人群中的 HDL-C 和 apoA1 水平以及冠状动脉粥样硬化的风险。我们对 24 名受试者的 ABCA1 基因 660 bp 5' 片段进行了测序，并鉴定了 3 个新的多态性：-477C/T、-419A/C 和 -320G/C。我们开发了检测方法，对前瞻性脂蛋白冠状动脉粥样硬化研究 (LCAS) 中的 372 名参与者进行了基因分型，并确定了变异与空腹血浆脂质以及在基线和随机分配氟伐他汀或安慰剂 2.5 年后获得的定量冠状动脉造影指数的关联。 -477C/T和-320G/C基因型分布分别为127个CC、171个CT和74个TT和130个GG、168个GC和75个CIC，并且处于完全连锁不平衡(P
Identification of mutations in the ATP binding cassette transporter (ABCA1) gene in patients with Tangier disease, who exhibit reduced HDL cholesterol (HDL-C) and apolipoprotein Al (apoA1) levels and premature coronary atherosclerosis, has led to the hypothesis that common polymorphisms in the ABCA1 gene could determine HDL-C and apoA1 levels and the risk of coronary atherosclerosis in the general population. We sequenced a 660-bp 5 ' fragment of the ABCA1 gene in 24 subjects and identified 3 novel polymorphisms: -477C/T, -419A/C, and -320G/C. We developed assays, genotyped 372 participants in the prospective Lipoprotein Coronary Atherosclerosis Study (LCAS), and determined the association of the variants with fasting plasma lipids and indices of quantitative coronary angiograms obtained at baseline and 2.5 years after randomization to fluvastatin or placebo. Distribution of -477C/T and -320G/C genotypes were 127 CC, 171 CT, and 74 TT and 130 GG, 168 GC, and 75 CIC, respectively, and were in complete linkage disequilibrium (P