Genetic variation of the transcription factor GATA3, not STAT4, is associated with the risk of type 2 diabetes in the Bangladeshi population

Type 2 diabetes mellitus is a multifactorial metabolic disorder caused by environmental factors and has a strong association with hereditary issues. These hereditary issues result in an imbalance in CD4+T cells and a decreased level of naïve CD4+T cells, which may be critical in the pathogenesis of type 2 diabetes. Transcription factors GATA3 and STAT4 mediate the cytokine-induced development of naïve T cells into Th1 or Th2 types. In the present study, genetic analyses of GATA3 SNP rs3824662 and STAT4 SNP rs10181656 were performed to investigate the association of allelic and genotypic variations with the risk of T2D in the Bangladeshi population. A total of 297 unrelated Bangladeshi patients with type 2 diabetes and 247 healthy individuals were included in the study. The allelic and genotypic frequencies of rs10181656 located in the STAT4 gene were not found to be associated with risk of type 2 diabetes. The GATA3 rs3824662 T allele and mutant TT genotype had a significant association with the risk of T2D [OR: 1.52 (1.15–2.02), X2 = 8.66, p = 0.003 and OR: 2.98 (1.36–6.55), X2 = 7.98, p = 0.04, respectively]. Thus, the present study postulates that the genetic variation of the transcription factor GATA3, not STAT4, is associated with the risk of type 2 diabetes in the Bangladeshi population.

2型糖尿病(Type 2 diabetes mellitus)是一类由环境因素诱发的多因素代谢紊乱性疾病，与遗传因素存在密切关联。此类遗传异常会引发CD4+T细胞失衡以及初始CD4+T细胞(naïve CD4+T cells)水平降低，该现象可能在2型糖尿病的发病机制中发挥关键作用。转录因子GATA3与STAT4可介导细胞因子诱导初始T细胞分化为Th1型或Th2型细胞的过程。本研究针对GATA3基因单核苷酸多态性(SNP, single nucleotide polymorphism) rs3824662与STAT4基因SNP rs10181656开展遗传分析，以探究孟加拉国人群中等位基因与基因型变异与2型糖尿病(T2D)患病风险的关联。本研究共纳入297名无亲缘关系的孟加拉国2型糖尿病患者，以及247名健康对照个体。位于STAT4基因的rs10181656位点的等位基因及基因型频率，未被发现与2型糖尿病患病风险存在显著关联。GATA3基因rs3824662位点的T等位基因与突变型TT基因型，均与2型糖尿病(T2D)患病风险存在显著关联[比值比(OR, odds ratio): 1.52（95%置信区间1.15~2.02），卡方值χ²=8.66，p=0.003；以及OR: 2.98（95%置信区间1.36~6.55），χ²=7.98，p=0.04]。据此，本研究提出假说：在孟加拉国人群中，转录因子GATA3的遗传变异而非STAT4的遗传变异，与2型糖尿病的患病风险相关。