Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits
Variations with modest effects have an important role in the genetic background of type 2 diabetes and diabetes-related traits
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DOI：
10.1038/jhg.2012.110
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发表时间：
2012-12-01
影响因子：
3.5
通讯作者：
Kadowaki, Takashi
中科院分区：
文献类型：
--
作者：
Fujita, Hayato;Hara, Kazuo;Kadowaki, Takashi
本研究的目的是探索影响不大的变异(之前在欧洲人群中通过大规模荟萃分析确定)在日本人群中2型糖尿病(T2D)和糖尿病相关特征的遗传背景中所起的作用。我们招募了2632名患有T2D的日本受试者和2050名非糖尿病受试者。我们分析了9个单核苷酸多态性(SNPs)，包括rs340874(PROX1)、rs4607517(GCK)、rs2191349(DGKB-TMEM195)、rs7034200(GLIS3)、rs10885122(ADRA2A)、rs174550(FADS1)、rs11605924(CRY2)、rs10830963(MTNR1B)和rs35767(IGF1)。Rs340874(PROX1)和rs174550(FADS1)与T2D显著相关(P=0.0078，OR：1.12；P=0.0071，OR：1.12)。与9个SNPs相关的风险等位基因较多的人患T2D的风险增加(P=0.0017)，空腹血糖水平较高(P=0.018)，糖化血红蛋白(1c)水平较高(P=0.013)，HOMA-β水平较低(P=0.033)。在日本人群中，我们发现FADS1的SNP和PROX1附近的SNP与T2D显著相关。目前的发现表明，与仅评估显着的SNPs相比，包含有增加疾病风险的SNPs更能捕捉T2D的遗传背景。《人类遗传学杂志》(2012年)57776-779；doi：10.1038/jhg.2012.110；2012年9月20日在线发布
The aim of the present study was to explore the role of variations with modest effects (previously identified by a large-scale meta-analysis in European populations) in the genetic background of type 2 diabetes (T2D) and diabetes-related traits in a Japanese population. We enrolled 2632 Japanese subjects with T2D and 2050 non-diabetic subjects. We analyzed nine single-nucleotide polymorphisms (SNPs), including rs340874 (PROX1), rs4607517 (GCK), rs2191349 (DGKB-TMEM195), rs7034200 (GLIS3), rs10885122 (ADRA2A), rs174550 (FADS1), rs11605924 (CRY2), rs10830963 (MTNR1B) and rs35767 (IGF1). rs340874 (PROX1) and rs174550 (FADS1) were significantly associated with T2D (P = 0.0078, OR: 1.12; and P = 0.0071, OR: 1.12, respectively). Subjects with more risk alleles related to nine SNPs had an increased risk of T2D (P = 0.0017), as well as a higher fasting plasma glucose level (P = 0.018), higher HbA(1c) level (P = 0.013) and lower HOMA-beta (P = 0.033) compared with subjects who had fewer risk alleles. We identified a significant association of a SNP of FADS1 and a SNP near PROX1 with T2D in a Japanese population. The present findings suggest that inclusion of SNPs with a tendency to increase the disease risk captured more of the genetic background of T2D than that revealed by only assessing significant SNPs. Journal of Human Genetics (2012) 57, 776-779; doi:10.1038/jhg.2012.110; published online 20 September 2012