The-1535 promoter variant of the visfatin gene is associated with serum triglyceride and HDL-cholesterol levels in Japanese subjects
The-1535 promoter variant of the visfatin gene is associated with serum triglyceride and HDL-cholesterol levels in Japanese subjects
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DOI：
10.1507/endocrj.k07e-039
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发表时间：
2008-02-01
影响因子：
2
通讯作者：
Yamagata, Kazuya
中科院分区：
文献类型：
--
作者：
Tokunaga, Ayumi;Miura, Atsuko;Yamagata, Kazuya
内脏脂肪素是一种新型的脂肪细胞因子，由内脏脂肪细胞表达。我们研究了内脂素基因的遗传变异在2型糖尿病的病理生理学和日本受试者的临床变量中的作用。采用PCR直接测序法对内脂素基因的11个外显子和启动子区进行单核苷酸多态性（SNP）筛查。在启动子区（SNP -1535 T> C）、外显子2（SNP + 131 C > G，Thr 44 Arg）和外显子7（SNP +903 G> A）发现了SNP。在200-448例糖尿病患者和200-333例对照组中，这些SNPs的等位基因和基因型频率无显著性差异。然而，在非糖尿病受试者中，-1535T/T基因型与较低的血清甘油三酯水平（T/T vs. T/C + C/C（p = 0.015）和T/T vs. C/C（p = 0.043））和较高的HDL-胆固醇水平（T/T vs. C/C，p=0.0496）相关。3 T3-L1脂肪细胞报告基因分析显示，-1535T和-1535C的启动子活性相似，表明观察到的关联可能反映了内脂素基因的致病变异与-1535T > C之间的连锁不平衡。
Visfatin is a novel adipocytokine that is expressed by the visceral fat cells. We investigated the role of genetic variation in the visfatin gene in the pathophysiology of type 2 diabetes and clinical variables in Japanese subjects. The 11 exons, and the promoter region of the visfatin gene were screened for single nucleotide polymorphisms (SNPs) by PCR-direct sequencing. We found SNPs in the promoter region (SNP - 1535T > C), exon 2 (SNP + 131 C > G, Thr44Arg), and exon 7 (SNP + 903G > A). The allele and genotype frequencies of these SNPs showed no significant differences between 200-448 diabetic and 200-333 control subjects. However, the -1535T/T genotype was associated with lower serum triglyceride levels (T/T vs. T/C + C/C (p = 0.015) and T/T vs. C/C (p = 0.043)) and higher HDL-cholesterol levels (T/T vs. C/C, p=0.0496) in the nondiabetic subjects. Reporter gene assay of 3T3-L1 adipocytes revealed that the promoter activity of -1535T and -1535C was similar, suggesting that the observed association may reflect linkage disequilibrium between -1535T > C and causative variations of the visfatin gene.