Variants of the PPARG, IGF2BP2, CDKAL1, HHEX, and TCF7L2 Genes Confer Risk of Type 2 Diabetes Independently of BMI in the German KORA Studies
Variants of the PPARG, IGF2BP2, CDKAL1, HHEX, and TCF7L2 Genes Confer Risk of Type 2 Diabetes Independently of BMI in the German KORA Studies
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DOI：
10.1055/s-2008-1078730
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发表时间：
2008-10-01
影响因子：
2.2
通讯作者：
Illig, T.
中科院分区：
文献类型：
--
作者：
Herder, C.;Rathmann, W.;Illig, T.
全基因组关联(GWA)研究确定了与2型糖尿病相关的新基因变异。然而，结果在不同的人群中并不总是一致的。因此，这项研究的目的是(I)利用德国KORA 500K糖尿病项目的数据，在主要北欧人群中复制以前GWA研究的结果，以及(Ii)评估BMI对单核苷酸多态(SNPs)和2型糖尿病之间关系的影响。KORA 500K糖尿病项目包括来自两个以人群为基础的KORA调查的433名确诊2型糖尿病患者和1438名非糖尿病对照。使用Affymetrix基因芯片人类映射500K阵列集进行基因分型。我们在10个基因中调查了SNPs与2型糖尿病的关联，这些基因被报道增加了2型糖尿病的风险，或者与这些变异处于完全或接近完全的连锁不平衡。CDKAL1基因的SNP与2型糖尿病的关联最强[年龄和性别调整后的优势比(OR)：1.3-1.39，p值0.0008-0.0004]。此外，我们还发现了PPARG、IGF2BP2、HHEX、TCF7L2和FTO基因中的SNPs与2型糖尿病关联的证据，其方向与前面描述的相同(p
Genome-wide association (GWA) studies identified novel gene variants that are associated with type 2 diabetes. However, results were not always consistent across different populations. Thus, the aims of this study were (i) to replicate findings from previous GWA studies in mainly Northern European populations using data from the German KORA 500K diabetes project and (ii) to assess the impact of BMI on associations between single nucleotide polymorphisms (SNPs) and type 2 diabetes. The KORA 500 K diabetes project includes 433 cases with validated type 2 diabetes and 1438 nondiabetic controls from two population-based KORA surveys. Genotyping was performed using the Affymetrix GeneChip Human Mapping 500K Array Set. We investigated associations between SNPs and type 2 diabetes in 10 genes that have been reported to increase the risk of type 2 diabetes or were in complete or near-complete linkage disequilibrium with these variants. SNPs in the CDKAL1 gene showed the strongest association with type 2 diabetes [range of age and sex-adjusted odds ratios (OR): 1.30-1.39, p-values 0.0008-0.0004]. In addition, we found evidence for association of SNPs in the genes PPARG, IGF2BP2, HHEX, TCF7L2, and FTO with type 2 diabetes in the same directions as previously described (p