5′ flanking variants of resistin are associated with obesity
5′ flanking variants of resistin are associated with obesity
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DOI：
10.2337/diabetes.51.5.1629
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发表时间：
2002-05-01
期刊：
影响因子：
7.7
通讯作者：
Hudson, TJ
中科院分区：
文献类型：
--
作者：
Engert, JC;Vohl, MC;Hudson, TJ
糖尿病和肥胖早就被认为是相关的。最近特征化的脂肪细胞激素foam（也称为FIZZ 3/ADSF）被认为是小鼠中糖耐量受损（IGT）和肥胖之间的分子联系。在人类cDNAn基因座的序列变异搜索确定了9个单核苷酸多态性（SNP），但没有编码变异。对这些SNP与糖尿病和肥胖症的关联的研究揭示了两个5'侧翼变体（g.第537章G 420），在强连锁不平衡，与BMI相关。在来自魁北克市地区和魁北克的Saguenay-Lac-St-Jean地区的非糖尿病个体中，g.- 537突变（等位基因频率= 0.04）与BMI增加显著相关（分别为P = 0.03和P = 0.01）。当这两个群体的数据结合起来，并根据年龄和性别进行调整时，537（比值比[OR] 2.72，95%CI 1.28-5.81）; 420个变异（1.58，1.06-2.35）与BMI大于或等于30 kg/m2的风险增加相关。相反，在斯堪的纳维亚的病例/对照和基于家庭的研究人群中，我们没有看到这些启动子变体对BMI的影响。在任何人群样本中均未发现与糖尿病相关。
Diabetes and obesity have long been known to be related. The recently characterized adipocyte hormone resistin (also called FIZZ3/ADSF) has been implicated as a molecular link between impaired glucose tolerance (IGT) and obesity in mice. A search for sequence variants at the human resistin locus identified nine single-nucleotide polymorphisms (SNPs) but no coding variants. An investigation into the association of these SNPs with diabetes and obesity revealed two 5' flanking variants (g.-537 and g.-420), in strong linkage disequilibrium, that are associated with BMI. In nondiabetic individuals from the Quebec City area and the Saguenay-Lac-St-Jean region of Quebec, the g.-537 mutation (allelic frequency = 0.04) was significantly associated with an increase in BMI (P = 0.03 and P = 0.01, respectively). When the data from these two populations were combined and adjusted for age and sex, both the g.-537 (odds ratio [OR] 2.72, 95% Cl 1.28-5.81) and the g.-420 variants (1.58, 1.06-2.35) were associated with an increased risk for a BMI greater than or equal to30 kg/m(2). In contrast, in case/control and family-based study populations from Scandinavia, we saw no effect on BMI with either of these promoter variants. No association was seen with diabetes in any of the population samples.