Souverein Olga W, Jukema J Wouter, Boekholdt S Matthijs, Zwinderman Aeilko H, Tanck Michael W T
Department of Clinical Epidemiology and Biostatistics, Academic Medical Center, Amsterdam, The Netherlands.
Eur J Hum Genet. 2005 Apr;13(4):445-51. doi: 10.1038/sj.ejhg.5201362.
The objective of this paper was to identify the single nucleotide polymorphisms (SNPs) that show unshared effects on plasma triglyceride (TG) levels and to investigate whether these SNPs show statistically independent effects on plasma TG levels. In total, 59 polymorphisms in 20 genes involved in lipid metabolism were investigated. Polymorphisms were selected for a multivariate ANOVA model if they showed an univariate association with TG (after adjustment for HDL-C and LDL-C) in more than 50% of bootstrap samples that were made from the original data. The multivariate model included 512 men with coronary artery disease from the REGRESS study who were completely genotyped for eight polymorphisms selected in the univariate procedure (ie, APOA1 G(-75)A, ABCA1 C(-477)T, ABCA1 G1051A, APOC3 T3206G, APOE Arg158Cys, LIPC C(-514)T, LPL Asn291Ser and LPL Ser447Stop). The gene variants APOA1 G(-75)A (P=0.04) and LPL Asn291Ser (P=0.03) were significantly associated with plasma TG levels in this multivariate analysis. The eight polymorphisms explained 8.9% of the variation in plasma TG levels. In conclusion, this study showed statistically independent effects of gene variants in the APOA1 and LPL genes on fasting plasma levels of TG. Nevertheless, only a small part of variation in TG levels could be explained by the polymorphisms.
本文的目的是识别对血浆甘油三酯（TG）水平有独特影响的单核苷酸多态性（SNP），并研究这些SNP对血浆TG水平是否具有统计学上的独立影响。总共对参与脂质代谢的20个基因中的59个多态性进行了研究。如果多态性在从原始数据生成的超过50%的自助抽样样本中显示与TG有单变量关联（在调整高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）之后），则将其选入多变量方差分析模型。多变量模型纳入了REGRESS研究中的512名冠心病男性患者，他们对在单变量程序中选择的8个多态性进行了完全基因分型（即载脂蛋白A1（APOA1）G（-75）A、ATP结合盒转运体A1（ABCA1）C（-477）T、ABCA1 G1051A、载脂蛋白C3（APOC3）T3206G、载脂蛋白E（APOE）Arg158Cys、肝脂酶（LIPC）C（-514）T、脂蛋白脂肪酶（LPL）Asn291Ser和LPL Ser447Stop）。在这项多变量分析中，基因变异APOA1 G（-75）A（P = 0.04）和LPL Asn291Ser（P = 0.03）与血浆TG水平显著相关。这8个多态性解释了血浆TG水平变异的8.9%。总之，本研究显示APOA1和LPL基因中的基因变异对空腹血浆TG水平具有统计学上的独立影响。然而，TG水平的变异中只有一小部分可由这些多态性解释。
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