Department of Biological Sciences, Faculty of Science, Kuwait University, PO Box 5069, Safat 13060, Kuwait.
BMC Med Genet. 2013 Sep 12;14:90. doi: 10.1186/1471-2350-14-90.
APOAI, a member of the APOAI/CIII/IV/V gene cluster on chromosome 11q23-24, encodes a major protein component of HDL that has been associated with serum lipid levels. The aim of this study was to determine the genetic association of polymorphisms in the APOAI promoter region with plasma lipid levels in a cohort of healthy Kuwaiti volunteers.
A 435 bp region of the APOAI promoter was analyzed by re-sequencing in 549 Kuwaiti samples. DNA was extracted from blood taken from 549 healthy Kuwaiti volunteers who had fasted for the previous 12 h. Univariate and multivariate analysis was used to determine allele association with serum lipid levels.
The target sequence included a partial segment of the promoter region, 5'UTR and exon 1 located between nucleotides -141 to +294 upstream of the APOAI gene on chromosome 11. No novel single nucleotide polymorphisms (SNPs) were observed. The sequences obtained were deposited with the NCBI GenBank with accession number [GenBank: JX438706]. The allelic frequencies for the three SNPs were as follows: APOAI rs670G = 0.807; rs5069C = 0.964; rs1799837G = 0.997 and found to be in HWE. A significant association (p < 0.05) was observed for the APOAI rs670 polymorphism with increased serum LDL-C. Multivariate analysis showed that APOAI rs670 was an independent predictive factor when controlling for age, sex and BMI for both LDL-C (OR: 1.66, p = 0.014) and TC (OR: 1.77, p = 0.006) levels.
This study is the first to report sequence analysis of the APOAI promoter in an Arab population. The unexpected positive association found between the APOAI rs670 polymorphism and increased levels of LDL-C and TC may be due to linkage disequilibrium with other polymorphisms in candidate and neighboring genes known to be associated with lipid metabolism and transport.
APOAI 是染色体 11q23-24 上的 APOAI/CIII/IV/V 基因簇的成员，编码高密度脂蛋白（HDL）的主要蛋白成分，与血清脂质水平有关。本研究旨在确定 APOAI 启动子区域多态性与科威特健康志愿者队列中血浆脂质水平的遗传关联。
对 549 例科威特人样本的 APOAI 启动子区域进行了 435bp 重测序分析。从禁食 12 小时的 549 名科威特健康志愿者的血液中提取 DNA。采用单变量和多变量分析来确定等位基因与血清脂质水平的关联。
目标序列包括 APOAI 基因第 11 号染色体上的启动子区域、5'UTR 和外显子 1 的一部分，位于 -141 到 +294 核苷酸上游。未观察到新的单核苷酸多态性（SNP）。获得的序列已在 NCBI GenBank 中注册，注册号为 [GenBank：JX438706]。三个 SNP 的等位基因频率如下：APOAI rs670G=0.807；rs5069C=0.964；rs1799837G=0.997，且符合哈迪-温伯格平衡。APOAI rs670 多态性与血清 LDL-C 升高显著相关（p<0.05）。多变量分析显示，在控制年龄、性别和 BMI 后，APOAI rs670 是 LDL-C（OR：1.66，p=0.014）和 TC（OR：1.77，p=0.006）水平的独立预测因子。
本研究首次报道了阿拉伯人群 APOAI 启动子的序列分析。APOAI rs670 多态性与 LDL-C 和 TC 水平升高之间的意外正相关可能是由于与已知与脂质代谢和转运相关的候选基因和相邻基因的其他多态性的连锁不平衡所致。
