KCNQ1、CDKN2A/2B、CDKAL1、HHEX、MTNR1B、SLC30A8、TCF7L2和UBE2E2对泰国人群患2型糖尿病风险的影响。
Impact of KCNQ1, CDKN2A/2B, CDKAL1, HHEX, MTNR1B, SLC30A8, TCF7L2, and UBE2E2 on risk of developing type 2 diabetes in Thai population.
作者信息
Plengvidhya Nattachet, Chanprasert Chutima, Chongjaroen Nalinee, Yenchitsomanus Pa-Thai, Homsanit Mayuree, Tangjittipokin Watip
机构信息
Division of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
Research Division, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.
出版信息
BMC Med Genet. 2018 Jun 5;19(1):93. doi: 10.1186/s12881-018-0614-9.
BACKGROUND
Several type 2 diabetes (T2D) susceptibility loci identified via genome-wide association studies were found to be replicated among various populations. However, the influence of these loci on T2D in Thai population is unknown. The aim of this study was to investigate the influence of eight single nucleotide polymorphisms (SNPs) reported in GWA studies on T2D and related quantitative traits in Thai population.
METHODS
Eight SNPs in or near the KCNQ1, CDKN2A/2B, SLC30A8, HHEX, CDKAL1, TCF7L2, MTNR1B, and UBE2E2 genes were genotyped. A case-control association study comprising 500 Thai patients with T2D and 500 ethnically-matched control subjects was conducted. Associations between SNPs and T2D were examined by logistic regression analysis. The impact of these SNPs on quantitative traits was examined by linear regression among case and control subjects.
RESULTS
Five SNPs in KCNQ1 (rs2237892), CDK2A/2B (rs108116610, SLC30A8 (rs13266634), TCF7L2 (rs7903146) and MTNR1B (rs1387153) were found to be marginally associated with risk of developing T2D, with odds ratios ranging from 1.43 to 2.02 (p = 0.047 to 3.0 × 10-4) with adjustments for age, sex, and body mass index. Interestingly, SNP rs13266634 of SLC30A8 gene reached statistical significance after correcting for multiple testing (p = 0.0003) (p < 0.006 after Bonferroni correction). However, no significant association was detected between HHEX (rs1111875), CDKAL1 (rs7756992), or UBE2E2 (rs7612463) and T2D. We also observed association between rs10811661 and both waist circumference and waist-hip ratio (p = 0.007 and p = 0.023, respectively). In addition, rs13266634 in SLC30A8 was associated with glycated hemoglobin (p = 0.018), and rs7903146 in TCF7L2 was associated with high-density lipoprotein cholesterol level (p = 0.023).
CONCLUSION
Of the eight genes included in our analysis, significant association was observed between KCNQ1, CDKN2A/2B, SLC30A8, TCF7L2, and MTNR1B loci and T2D in our Thai study population. Of these, CDKN2A/2B, SLC30A8, and TCF7L2 genes were also significantly associated with anthropometric, glycemic and lipid characteristics. Larger cohort studies and meta-analyses are needed to further confirm the effect of these variants in Thai population.
背景
通过全基因组关联研究确定的几个2型糖尿病（T2D）易感基因座在不同人群中得到了重复验证。然而，这些基因座对泰国人群T2D的影响尚不清楚。本研究的目的是调查全基因组关联研究中报道的8个单核苷酸多态性（SNP）对泰国人群T2D及相关定量性状的影响。
方法
对KCNQ1、CDKN2A/2B、SLC30A8、HHEX、CDKAL1、TCF7L2、MTNR1B和UBE2E2基因内部或附近的8个SNP进行基因分型。开展了一项病例对照关联研究，纳入500例泰国T2D患者和500例种族匹配的对照者。通过逻辑回归分析检验SNP与T2D之间的关联。通过病例组和对照组的线性回归分析这些SNP对定量性状的影响。
结果
发现KCNQ1（rs2237892）、CDK2A/2B（rs108116610）、SLC30A8（rs13266634）、TCF7L2（rs7903146）和MTNR1B（rs1387153）中的5个SNP与发生T₂D的风险存在边缘关联，校正年龄、性别和体重指数后，比值比为1.43至2.02（P=0.047至3.0×10⁻⁴）。有趣的是，SLC30A8基因的SNP rs13266634在多重检验校正后达到统计学显著性（P=0.0003）（Bonferroni校正后P<0.006）。然而，未检测到HHEX（rs1111875）、CDKAL1（rs7756992）或UBE2E2（rs7612463）与T2D之间存在显著关联。我们还观察到rs10811661与腰围和腰臀比均相关（分别为P=0.007和P=0.023）。此外，SLC30A8中的rs13266634与糖化血红蛋白相关（P=0.018），TCF7L2中的rs7903146与高密度脂蛋白胆固醇水平相关（P=0.023）。
结论
在我们分析的8个基因中，在我们的泰国研究人群中观察到KCNQ1、CDKN2A/2B、SLC30A8、TCF7L2和MTNR1B基因座与T2D之间存在显著关联。其中，CDKN2A/2B、SLC30A8和TCF7L2基因也与人体测量、血糖和血脂特征显著相关。需要更大规模的队列研究和荟萃分析来进一步证实这些变异在泰国人群中的作用。
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