Liju Samuel, Chidambaram Manickam, Mohan Viswanathan, Radha Venkatesan
Department of Molecular Genetics, Madras Diabetes Research Foundation, Chennai 600086, India.
Dr. Mohan's Diabetes Specialties Centre, ICMR Centre for Diabetes Advanced Research and WHO Collaborating Centre for Non-communicable Diseases Prevention and Control, Chennai 600086, India.
Genomics Inform. 2020 Sep;18(3):e27. doi: 10.5808/GI.2020.18.3.e27. Epub 2020 Sep 9.
The prevalence of early-onset type 2 diabetes (EOT2D) is increasing in Asian countries. Genome-wide association studies performed in European and various other populations have identified associations of numerous variants with type 2 diabetes in adults. However, the genetic component of EOT2D which is still unexplored could have similarities with late-onset type 2 diabetes. Here in the present study we aim to identify the association of variants with EOT2D in South Indian population. Twenty-five variants from 18 gene loci were genotyped in 1,188 EOT2D and 1,183 normal glucose tolerant subjects using the MassARRAY technology. We confirm the association of the HHEX variant rs1111875 with EOT2D in this South Indian population and also the association of CDKN2A/2B (rs7020996) and TCF7L2 (rs4506565) with EOT2D. Logistic regression analyses of the TCF7L2 variant rs4506565(A/T), showed that the heterozygous and homozygous carriers for allele 'T' have odds ratios of 1.47 (95% confidence interval [CI], 1.17 to 1.83; p = 0.001) and 1.65 (95% CI, 1.18 to 2.28; p = 0.006) respectively, relative to AA homozygote. For the HHEX variant rs1111875 (T/C), heterozygous and homozygous carriers for allele 'C' have odds ratios of 1.13 (95% CI, 0.91 to 1.42; p = 0.27) and 1.58 (95% CI, 1.17 to 2.12; p = 0.003) respectively, relative to the TT homozygote. For CDKN2A/2B variant rs7020996, the heterozygous and homozygous carriers of allele 'C' were protective with odds ratios of 0.65 (95% CI, 0.51 to 0.83; p = 0.0004) and 0.62 (95% CI, 0.27 to 1.39; p = 0.24) respectively, relative to TT homozygote. This is the first study to report on the association of HHEX variant rs1111875 with EOT2D in this population.
早发型2型糖尿病（EOT2D）在亚洲国家的患病率正在上升。在欧洲和其他各种人群中进行的全基因组关联研究已经确定了许多变异与成人2型糖尿病的关联。然而，EOT2D尚未被探索的遗传成分可能与晚发型2型糖尿病有相似之处。在本研究中，我们旨在确定印度南部人群中变异与EOT2D的关联。使用MassARRAY技术对1188例EOT2D患者和1183例糖耐量正常的受试者进行了18个基因位点的25个变异的基因分型。我们证实了HHEX变异rs1111875与该印度南部人群的EOT2D有关联，以及CDKN2A/2B（rs7020996）和TCF7L2（rs4506565）与EOT2D的关联。对TCF7L2变异rs4506565（A/T）的逻辑回归分析表明，等位基因“T”的杂合子和纯合子携带者相对于AA纯合子的优势比分别为1.47（95%置信区间[CI]，1.17至1.83；p = 0.001）和1.65（95%CI，1.18至2.28；p = 0.006）。对于HHEX变异rs1111875（T/C），等位基因“C”的杂合子和纯合子携带者相对于TT纯合子的优势比分别为1.13（95%CI，0.91至1.42；p = 0.27）和1.58（95%CI，1.17至2.12；p = 0.003）。对于CDKN2A/2B变异rs7020996，等位基因“C”的杂合子和纯合子携带者相对于TT纯合子具有保护作用，优势比分别为0.65（95%CI，0.51至0.83；p = 0.0004）和0.62（95%CI，0.27至1.39；p = 0.24）。这是第一项报道HHEX变异rs1111875与该人群EOT2D关联的研究。
