A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle
A single nucleotide polymorphism in the FADS1/FADS2 gene is associated with plasma lipid profiles in two genetically similar Asian ethnic groups with distinctive differences in lifestyle
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DOI：
10.1007/s00439-010-0815-6
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发表时间：
2010-06-01
期刊：
影响因子：
5.3
通讯作者：
Iwamoto, Sadahiko
中科院分区：
文献类型：
--
作者：
Nakayama, Kazuhiro;Bayasgalan, Tumenbayer;Iwamoto, Sadahiko
最近的全基因组关联研究（GWASs）表明，FADS1/FADS2的单核苷酸多态性（snp）与欧洲血统人群的血脂浓度有关。我们研究了两个亚洲人群，即日本人和蒙古人，FADS1/FADS2 snp与血浆甘油三酯、高密度脂蛋白胆固醇（HDL-C）和低密度脂蛋白胆固醇（LDL-C）浓度之间的关系。rs174547 （T/C）基因型与GWAS中甘油三酯和HDL-C浓度相关，在21,004名日本人和1,203名蒙古人中进行了测定。采用多元线性回归模型评估基因型-表型相关性，假设遗传为加性模型。在日本人群中，rs174547c等位基因的拷贝数与甘油三酯水平升高（P = 1.5 × 10(-6)）和HDL-C水平降低（P = 0.03）显著相关。另一方面，在蒙古人群中，rs174547c等位基因拷贝数与LDL-C水平的降低密切相关（P = 2.6 × 10(-6)），但与甘油三酯和HDL-C水平无关。FADS1/FADS2位点周围snp的连锁不平衡模式和单倍型结构在日本人和蒙古人之间无显著差异。目前的数据表明，FADS1/FADS2基因座可以添加到亚洲人多基因血脂异常的基因座列表中。此外，FADS1/FADS2对亚洲人血浆脂质谱的不同影响可能与饮食中多不饱和脂肪酸摄入量的差异有关，多不饱和脂肪酸是FADS1/FADS2编码酶的底物。
Recent genome-wide association studies (GWASs) showed that single nucleotide polymorphisms (SNPs) in FADS1/FADS2 were associated with plasma lipid concentrations in populations with European ancestry. We investigated the associations between the SNPs in FADS1/FADS2 and plasma concentrations of triglycerides, high-density lipoprotein cholesterol (HDL-C), and low-density lipoprotein cholesterol (LDL-C) in two Asian groups, i.e., Japanese and Mongolians. The genotype of rs174547 (T/C), found to be associated with triglyceride and HDL-C concentrations in the GWAS, was determined in 21,004 Japanese and 1,203 Mongolian individuals. Genotype-phenotype association was assessed by using multiple linear regression models, assuming an additive model of inheritance. The copy number of the rs174547 C allele was significantly associated with increased triglyceride levels (P = 1.5 x 10(-6)) and decreased HDL-C levels (P = 0.03) in the Japanese population. On the other hand, in the Mongolian population, the rs174547 C allele copy number was strongly associated with decreased LDL-C levels (P = 2.6 x 10(-6)), but was not associated with triglyceride and HDL-C levels. The linkage disequilibrium pattern and haplotype structures of SNPs around the FADS1/FADS2 locus showed no marked dissimilarity between Japanese and Mongolian individuals. The present data indicate that the FADS1/FADS2 locus can be added to the growing list of loci involved in polygenic dyslipidemia in Asians. Furthermore, the variable effects of FADS1/FADS2 on plasma lipid profiles in Asians may result from differences in the dietary intake of polyunsaturated fatty acids, which serve as substrates for enzymes encoded by FADS1/FADS2.