Human resistin gene: molecular scanning and evaluation of association with insulin sensitivity and type 2 diabetes in Caucasians.
Human resistin gene: molecular scanning and evaluation of association with insulin sensitivity and type 2 diabetes in Caucasians.
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DOI：
10.1210/jcem.87.6.8528
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发表时间：
2002-06
期刊：
影响因子：
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通讯作者：
Hua Wang;W. Chu;C. Hemphill;S. Elbein
中科院分区：
文献类型：
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作者：
Hua Wang;W. Chu;C. Hemphill;S. Elbein
胰岛素抵抗与肥胖密切相关，但即使在肥胖人群中，胰岛素敏感性也存在很大差异。最近，一种新的脂肪细胞激素抵抗素被发现，显示减少胰岛素介导的葡萄糖摄取，并显示在肥胖小鼠中增加。我们利用19号染色体草图序列确定了人类抵抗素的基因组结构，并筛选了外显子、内含子和侧翼序列的变异。我们筛选了44名2型糖尿病患者和20名胰岛素敏感性极端的非糖尿病家庭成员。我们鉴定出8个非编码单核苷酸多态性（SNPs）和1个GAT微卫星重复序列。选择3个相互间不完全连锁不平衡且等位频率超过5%的snp进行进一步研究。没有SNP与2型糖尿病相关，但启动子区域的SNP是接受静脉糖耐量试验的非糖尿病家庭成员胰岛素敏感性指数的重要决定因素（P = 0.04）。三个常见snp作为胰岛素敏感性指数的决定因素与体重指数的交互作用有统计学意义（P < 0.01）。抵抗素基因中的非编码snp可能影响与肥胖相互作用的胰岛素敏感性，但这一发现需要在其他人群中得到证实。
Insulin resistance is strongly associated with obesity, but even among obese subjects insulin sensitivity varies widely. Recently, a new adipocyte hormone, resistin, was identified, shown to reduce insulin-mediated glucose uptake, and shown to be increased in obese mice. We used the chromosome 19 draft sequence to determine the genomic structure of human resistin and to screen the exons, introns, and flanking sequences for variation. We screened 44 subjects with type 2 diabetes and 20 nondiabetic family members who were at the extremes of insulin sensitivity. We identified eight noncoding single nucleotide polymorphisms (SNPs) and one GAT microsatellite repeat. Three SNPs, which were in incomplete linkage disequilibrium with each other and had allelic frequencies exceeding 5%, were selected for further study. No SNP was associated with type 2 diabetes, but the SNP in the promoter region was a significant determinant of insulin sensitivity index (P = 0.04) among nondiabetic family members who had undergone iv glucose tolerance tests. The three common SNPs showed statistical significance as determinants of insulin sensitivity index (P < 0.01) in interaction with body mass index. Noncoding SNPs in the resistin gene may influence insulin sensitivity in interaction with obesity, but this finding will need to be confirmed in other populations.