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Background  Evidence from genetic epidemiology indicates that type 2 diabetes (T2D) has a strong genetic basis. Activated  STAT4  has an inflammatory effect, and STAT4 is an important mediator of inflammation in diabetes. Our study aimed to study the association between STAT4 single nucleotide polymorphisms (SNPs) and T2D susceptibility in Chinese Han population.    Methods  We conducted a 'case–control' study among 500 T2D patients and 501 healthy individuals. 5 candidate  STAT4  SNPs were successfully genotyped. The association between SNPs and T2D susceptibility under different genetic models was evaluated by logistic regression analysis. ‘SNP-SNP’ interaction was analyzed and completed by multi-factor dimensionality reduction (MDR). Finally, we evaluated the differences of clinical characteristics under different genotypes by one-factor analysis of variance.    Results  The overall results showed that  STAT4  rs3821236 was associated with increasing T2D risk under allele (OR 1.23,  p  = 0.020), homozygous (OR 1.51,  p  = 0.025), dominant (OR 1.36,  p  = 0.029), and additive models (OR 1.23,  p  = 0.020). The results of stratified analysis showed that rs3821236, rs11893432, and rs11889341 were risk factors for T2D among participants ≤ 60 years old. Only rs11893432 was associated with increased T2D risk among female participants. There was also a potential association between rs3821236 and T2D with nephropathy risk. STAT4 rs11893432, rs7574865 and rs897200 were significantly associated with lysophosphatidic acid, cystatin C and thyroxine t4, respectively.    Conclusion  The genetic polymorphisms of STAT4 is potentially associated with T2D susceptibility of Chinese population. In particular, rs3821236 is significantly associated with T2D risk both in the overall and several subgroup analyses. Our study may provide new ideas for T2D individualized diagnosis/protection.    Supplementary Information  The online version contains supplementary material available at 10.1186/s12920-021-01000-2.

Association between STAT4 gene polymorphism and type 2 diabetes risk in Chinese Han population