Genome-wide linkage analysis of type 2 diabetes mellitus reconfirms the susceptibility locus on 11p13-p12 in Japanese
Genome-wide linkage analysis of type 2 diabetes mellitus reconfirms the susceptibility locus on 11p13-p12 in Japanese
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DOI：
10.1007/s10038-004-0199-3
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发表时间：
2004-11-01
影响因子：
3.5
通讯作者：
Sasazuki, T
中科院分区：
文献类型：
--
作者：
Nawata, H;Shirasawa, S;Sasazuki, T
2型糖尿病是一种异质性疾病，2型糖尿病的发生与胰岛素分泌缺陷和胰岛素抵抗有关。导致2型糖尿病的原发性代谢缺陷被认为在人群中是不同的，特别是在日本人和高加索人中。在这里，我们使用102个受影响的日本同胞对进行了2型糖尿病的全基因组扫描，以确定易患2型糖尿病的遗传因素。非参数连锁分析显示一个提示性证据与11 p13-p12连锁[D11 S905：两点最大LOD评分（MLS）为2.89，多点MLS为2.32]，一个名义上显著的证据与6 q15-q16连锁（D 6S 462：两点MLS为2.02）。有趣的是，11 p13-p12区域被报道是日本2型糖尿病的易感位点，提示有连锁证据，并且D11 S905与D11 S935在5 cM之内，在先前的连锁分析中具有最高的MLS。在包括本研究的3份报告中，唯一具有提示与日本2型糖尿病相关证据的重叠易感区域是D11 S935和D11 S905。这些结果表明，日本人2型糖尿病的易感基因位于11 p13-p12。
Type 2 diabetes mellitus is a heterogeneous disorder, and the development of type 2 diabetes mellitus is associated with both insulin secretion defect and insulin resistance. The primary metabolic defect leading to type 2 diabetes mellitus has been thought to be varied among populations, especially in Japanese and Caucasians. Here, we have done the genome-wide scan for type 2 diabetes mellitus using 102 affected Japanese sib-pairs to identify the genetic factors predisposing to type 2 diabetes mellitus. Nonparametric linkage analysis showed one suggestive evidence for linkage to 11p13-p12 [D11S905: two-point maximum LOD score (MLS) of 2.89 and multipoint MLS of 2.32] and one nominally significant evidence for linkage to 6q15-q16 (D6S462: two-point MLS of 2.02). Interestingly, the 11p13-p12 region was reported to be a susceptibility locus for Japanese type 2 diabetes mellitus with suggestive evidence of linkage, and D11S905 was within 5 cM to D11S935 with the highest MLS in the previous linkage analysis reported. The only overlapped susceptibility region with suggestive evidence of linkage for Japanese type 2 diabetes mellitus was D11S935 D11S905 among the three reports including this study. These results taken together suggest that a susceptibility gene for type 2 diabetes mellitus in Japanese will reside in 11p13-p12.