Molecular screening and association analyses of the interleukin 6 receptor gene variants with type 2 diabetes, diabetic nephropathy, and insulin sensitivity
Molecular screening and association analyses of the interleukin 6 receptor gene variants with type 2 diabetes, diabetic nephropathy, and insulin sensitivity
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DOI：
10.1210/jc.2004-1606
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发表时间：
2005-02-01
影响因子：
5.8
通讯作者：
Elbein, SC
中科院分区：
文献类型：
--
作者：
Wang, H;Zhang, ZX;Elbein, SC
IL-6水平和多态性与2型糖尿病（T2 DM）和胰岛素抵抗有关。IL-6受体（IL-6 R）包含两个亚基，IL-6 R和gp 130，其中L-6 R赋予IL-6作用特异性，并位于染色体1 q21上与T2 DM复制连锁的区域。我们在北方欧洲高加索人和非洲裔美国人族群中筛选了该基因的变异。我们鉴定了11个次要等位基因频率超过5%的变体，包括两个氨基酸变化（D358 A和V3851）和3'非翻译区中的四个变体。没有变异与肥胖或胰岛素敏感性指标相关，但3'非翻译区的两个单核苷酸多态性在所有高加索人中显示出与2型糖尿病相关的趋势，包括D358 A在内的三个单核苷酸多态性在北方欧洲高加索人中显示出与2型糖尿病相关的趋势（P < 0.06）。V385 I变异是非洲裔美国人特有的，与糖尿病和糖尿病肾病显著相关（P < 0.05）。在转录序列中的四个变体的杂合个体中，一个等位基因显著过度表达，从而表明存在控制mRNA稳定性或表达的调节变体。IL-6 R不太可能解释该区域与糖尿病的联系，但我们的工作支持变体在T2 DM风险中的次要作用，并表明序列变体可能改变IL-6 R mRNA水平和可溶性IL-6 R水平。
IL-6 levels and polymorphisms have been implicated in type 2 diabetes mellitus (T2DM) and insulin resistance. The IL-6 receptor (IL-6R) comprises two subunits, IL-6R and gp130, of which L-6R confers specificity to IL-6 action and is located in a region of replicated linkage to T2DM on chromosome 1q21. We screened this gene for variation in Northern European Caucasian and African-American ethnic groups. We identified 11 variants with a minor allele frequency over 5%, including two amino acid changes (D358A and V3851) and four variants in the 3' untranslated region. No variant was associated with obesity or measures of insulin sensitivity, but two single nucleotide polymorphisms in the 3' untranslated region showed a trend to an association with T2DM in all Caucasians, and three single nucleotide polymorphisms, including D358A, showed a trend (P < 0.06) to an association with T2DM among the subset of Northern European Caucasians. Variant V385I was unique to African-Americans and was significantly associated with diabetes and diabetic nephropathy (P < 0.05). Among individuals heterozygous for the four variants in the transcribed sequence, one allele was significantly overrepresented, thus suggesting the existence of a regulatory variant controlling mRNA stability or expression. IL-6R is not likely to explain the linkage to diabetes in this region, but our work supports a minor role of variants in T2DM risk and suggests that sequence variants may alter IL-6R mRNA levels and possibly levels of soluble IL-6R.