Department of Medicine and Therapeutics, The Chinese University of Hong Kong, Shatin, Hong Kong, SAR, China.
Atherosclerosis. 2010 Feb;208(2):427-32. doi: 10.1016/j.atherosclerosis.2009.08.013. Epub 2009 Aug 15.
Familial combined hyperlipidaemia (FCH) is the most common genetic dyslipidaemia associated with coronary artery disease. Single nucleotide polymorphisms (SNPs) and haplotypes in the APOA1/C3/A4/A5 gene cluster are associated with FCH in Caucasians and with elevated triglycerides (TG) in various ethnic groups. We examined these associations with FCH in Hong Kong Chinese.
Fifty-six Chinese FCH patients and 176 unrelated controls were studied. Thirteen SNPs in the APOA1/C3/A4/A5 cluster were genotyped.
Four alleles in APOA5 were associated with FCH (P<0.001). The -1131T>C (rs662799) and -3A>G (rs651821) SNPs in APOA5 were in almost complete linkage disequilibrium (LD, r(2)=0.99), and their minor alleles were more frequent (P<0.001) in FCH than controls (0.60 vs. 0.24). The odds ratio (OR) for FCH was 6.2 (95% CI, 2.6-14.8) and 6.1 (2.6-14.6) per copy of -1131C and -3G, respectively, and 24.6 (8.4-72.0) and 24.4 (8.4-70.9) in -1131C and -3G homozygotes, respectively, as compared to wild-type homozygotes. The 1891T>C (rs2266788) SNP was in LD (r(2)=0.68) with -1131T>C and -3A>G, and the minor allele was more frequent in FCH than controls (0.42 vs. 0.19, P<0.001). The 553G>T (rs2075291) nonsynonymous variant was also associated with FCH (0.15 vs. 0.04, P=0.001) and, along with -3A>G (or -1131T>C) and 1891T>C, contributed to haplotypes predicting FCH. The two tightly linked SNPs, -1131T>C and -3A>G polymorphism were significantly associated with lipid traits in all subjects combined, with variant homozygous subjects having higher TG and LDL-C and lower HDL-C levels.
Some common polymorphisms and haplotypes in APOA5 are closely associated with FCH in Hong Kong Chinese, and these differ from those found in Caucasians.
家族性复合型高脂血症（FCH）是与冠状动脉疾病相关的最常见的遗传性血脂异常。载脂蛋白 A1/C3/A4/A5 基因簇中的单核苷酸多态性（SNPs）和单倍型与高加索人群中的 FCH 以及不同种族人群中的甘油三酯（TG）升高有关。我们研究了这些与香港华人 FCH 的关联。
研究了 56 例中国 FCH 患者和 176 例无关对照。对载脂蛋白 A1/C3/A4/A5 簇中的 13 个 SNPs 进行了基因分型。
APOA5 中的 4 个等位基因与 FCH 相关（P<0.001）。APOA5 中的 -1131T>C(rs662799)和 -3A>G(rs651821)SNP 几乎完全连锁不平衡（LD，r(2)=0.99），其较小等位基因在 FCH 患者中比对照组更为常见（P<0.001）（0.60 对 0.24）。-1131C 和 -3G 每拷贝的 FCH 比值比（OR）分别为 6.2（95%CI，2.6-14.8）和 6.1（2.6-14.6），-1131C 和 -3G 纯合子的比值比分别为 24.6（8.4-72.0）和 24.4（8.4-70.9），与野生型纯合子相比。1891T>C(rs2266788)SNP 与-1131T>C 和 -3A>G 连锁不平衡（r(2)=0.68），较小等位基因在 FCH 患者中比对照组更为常见（0.42 对 0.19，P<0.001）。553G>T(rs2075291)错义变异也与 FCH 相关（0.15 对 0.04，P=0.001），与-3A>G（或-1131T>C）和 1891T>C 一起，有助于预测 FCH 的单倍型。在所有受试者中，这两个紧密连锁的 SNP（-1131T>C 和 -3A>G 多态性）与血脂特征显著相关，变异纯合子受试者的 TG 和 LDL-C 水平较高，HDL-C 水平较低。
APOA5 中的一些常见多态性和单倍型与香港华人的 FCH 密切相关，与高加索人群中的发现不同。
