STAT4 Gene Polymorphism in Children with Type-1 Autoimmune Hepatitis

Abstract

Background: The signal transducer and activator of the transcription 4 (STAT4) gene plays an important role in macrophages, dendritic cells, activated peripheral blood monocytes, and Th1-dependent liver injury.

AIM: To assess the association of signal transducer and activator of transcription (STAT4) single gene polymorphisms (SNPs) (rs7574865, rs7582694) with type-1 autoimmune hepatitis (AIH) in Egyptian children.

MATERIALS AND METHODS: 125 children diagnosed as AIH type-1and 125 control healthy children were included for genotyping of STAT4 SNPs (rs7574865 and rs7582694).

Results: STAT4 (rs7574865) GT and TT genotypes increased the risk of AIH type-1 development by 2 and 4 folds regarding the GG genotype (p < 0.019, 0.001 respectively). T allele individuals had about 2.5 folds increased risk of the disease compared to those with G allele (p < 0.001). STAT4 (rs7582694) GC and CC genotypes increased the risk of AIH type-1 by 1.76 and 3.8 folds regarding the GG genotype (p < 0.037, 0.015 respectively). The C allele had about 1.88 folds increased risk of AIH type-1 development than those with the G allele (p = 0.002). Dominant model of either SNPs and the recessive model of rs7574865 only are significant predictors of AIH type-1.

Conclusion: Minor alleles of both STAT4 SNPs (rs7574865 T allele, rs7582694 C allele) are associated with an increased risk of type-1 AIH. The disease could be predicted by the dominant model of either SNPs and by the recessive model of rs7574865.