Choi Jung Ran, Nam Chung Mo, Kang Dae Ryong, Eom Sang Mi, Lee Hye Jin, Park Chan Mi, Im Jin Woo, Jang Yangsoo
Department of Cardiology, Yonsei University College of Medicine, 250 Seongsanno, Sudaemun-gu, Seoul 120-752, Korea.
Yonsei Med J. 2007 Aug 31;48(4):609-18. doi: 10.3349/ymj.2007.48.4.609.
Recent studies using human and mice reported that apolipoprotein A-V (APOA5) gene plays an important role in controlling triglyceride (TG) concentrations. The purpose of the present study was to investigate the correlation between single nucleotide polymorphisms (SNPs) and haplotypes in the APOA5 gene and TG in subjects and to search for possible associations of the APOA5 gene variants and common haplotypes with hypertriglyceridemia (HTG).
We examined the case-control subjects including 100 HTG patients and 243 unrelated healthy control. The genes were screened for SNPs by direct sequencing in 48 genetically unrelated individuals. Six SNPs (-1390C>T, -1020G>A, -3A>G, V150M, G182C and 1259T>C) were genotyped in case and control populations.
In this study, our results indicated a strong association between APOA5 SNP -3A>G and G182C and elevated TG levels (p<0.001). Analysis of the SNPs from APOA5 gene has identified major haplotype showing very strong association with HTG, CGGGTT (p<0.001). Likelihood ratio test (LRT) of these six SNPs revealed that haplotypes were strong independent predictors of HTG (p<0.001). Haplotype-trend logistic regression (HTR) analysis revealed a significant association between the CGGGGC (haplotype 2) and CGGGTT (haplotype 4) and HTG (OR=2.48, 95% CI=1.06-5.76 and OR=8.54, 95% CI=2.66-27.42, respectively).
We confirm that the APOA5 variants are associated with triglyceride levels and the haplotype may be strong independent predictors of HTG among Koreans.
近期使用人类和小鼠进行的研究表明，载脂蛋白A-V（APOA5）基因在控制甘油三酯（TG）浓度方面发挥着重要作用。本研究的目的是调查APOA5基因中的单核苷酸多态性（SNP）和单倍型与受试者TG之间的相关性，并寻找APOA5基因变异和常见单倍型与高甘油三酯血症（HTG）之间的可能关联。
我们检查了病例对照受试者，包括100名HTG患者和243名无亲缘关系的健康对照。通过对48名无亲缘关系个体进行直接测序来筛选基因中的SNP。在病例组和对照组人群中对六个SNP（-1390C>T、-1020G>A、-3A>G、V150M、G182C和1259T>C）进行基因分型。
在本研究中，我们的结果表明APOA5 SNP -3A>G和G182C与TG水平升高之间存在强关联（p<0.001）。对APOA5基因SNP的分析确定了与HTG显示出非常强关联的主要单倍型CGGGTT（p<0.001）。这六个SNP的似然比检验（LRT）表明，单倍型是HTG的强独立预测因子（p<0.001）。单倍型趋势逻辑回归（HTR）分析显示，CGGGGC（单倍型2）和CGGGTT（单倍型4）与HTG之间存在显著关联（OR分别为2.48，95%CI=1.06-5.76和OR=8.54，95%CI=2.66-27.42）。
我们证实APOA5变异与甘油三酯水平相关，并且该单倍型可能是韩国人群中HTG的强独立预测因子。
