Tokunaga Ayumi, Miura Atsuko, Okauchi Yukiyoshi, Segawa Katsumori, Fukuhara Atsunori, Okita Kohei, Takahashi Masahiko, Funahashi Tohru, Miyagawa Jun-Ichiro, Shimomura Iichiro, Yamagata Kazuya
Department of Metabolic Medicine, Graduate School of Medicine, Osaka University, Japan.
Endocr J. 2008 Mar;55(1):205-12. doi: 10.1507/endocrj.k07e-039. Epub 2008 Feb 13.
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 + 131C>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.
内脂素是一种由内脏脂肪细胞表达的新型脂肪细胞因子。我们研究了内脂素基因的遗传变异在2型糖尿病病理生理学及日本受试者临床变量中的作用。通过聚合酶链反应直接测序法对内脂素基因的11个外显子和启动子区域进行单核苷酸多态性（SNP）筛查。我们在启动子区域（SNP - 1535T>C）、外显子2（SNP + 131C>G，苏氨酸44精氨酸）和外显子7（SNP + 903G>A）中发现了SNP。这些SNP的等位基因和基因型频率在200 - 448例糖尿病患者和200 - 333例对照受试者之间无显著差异。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相关（T/T vs. T/C + C/C（p = 0.015）以及T/T vs. C/C（p = 0.043））和较高的高密度脂蛋白胆固醇水平（T/T vs. C/C，p = 0.0496）。对3T3 - L1脂肪细胞进行的报告基因检测显示，-1535T和-1535C的启动子活性相似，这表明观察到的关联可能反映了-1535T>C与内脂素基因致病变异之间的连锁不平衡。
