Latvian Biomedical Research and Study Centre, Ratsupites Street 1, LV-1067 Riga, Latvia.
Gene. 2013 Sep 25;527(2):462-8. doi: 10.1016/j.gene.2013.06.079. Epub 2013 Jul 13.
Variations in the FTO gene and near the TMEM18 gene are risk factors for common form of obesity, but have also been linked with type 2 diabetes (T2D). Our aim was to investigate the contribution of these variants to risk of T2D in a population in Latvia. Four single nucleotide polymorphisms (SNP) in the first and fourth intronic regions of FTO and one close to TMEM18 were genotyped in 987 patients with T2D and 1080 controls selected from the Latvian Genome Data Base (LGDB). We confirmed association of SNPs in the first intron (rs11642015, rs62048402 and rs9939609) of FTO and rs7561317 representing the TMEM18 locus with T2D. Association between SNP in FTO and T2D remained significant after correction for body mass index (BMI). The rs57103849 located in the fourth intron of FTO and rs7561317 in TMEM18 showed BMI independent association with younger age at diagnosis of T2D. Our results add to the evidence that BMI related variants in and near FTO and TMEM18 may increase the risk for T2D not only through secondary effects of obesity. The influence of variants in the fourth intron of the FTO gene on development of T2D may be mediated by mechanisms other than those manifested by SNPs in the first intron of the same gene.
FTO 基因和 TMEM18 基因附近的变异是普通肥胖形式的风险因素,但也与 2 型糖尿病(T2D)有关。我们的目的是研究这些变体在拉脱维亚人群中对 T2D 风险的贡献。在从拉脱维亚基因组数据库(LGDB)中选择的 987 名 T2D 患者和 1080 名对照中,对 FTO 的第一个和第四个内含子区域中的四个单核苷酸多态性(SNP)和一个靠近 TMEM18 的 SNP 进行了基因分型。我们证实了 FTO 第一个内含子(rs11642015、rs62048402 和 rs9939609)和代表 TMEM18 基因座的 rs7561317 的 SNP 与 T2D 之间存在关联。在对体重指数(BMI)进行校正后,FTO 与 T2D 之间的关联仍然显著。位于 FTO 第四内含子中的 rs57103849 和 TMEM18 中的 rs7561317 与 T2D 诊断时的年龄呈 BMI 独立相关。我们的结果增加了证据,即 FTO 和 TMEM18 内和附近的 BMI 相关变体不仅通过肥胖的二次效应,还可能增加 T2D 的风险。FTO 基因第四内含子中的变体对 T2D 的影响可能通过与同一基因第一内含子中的 SNP 不同的机制来介导。