Association of  STAT4  and  PTPN22  polymorphisms and their interactions with type-1 autoimmune hepatitis susceptibility in Chinese Han children

Xiaofeng Li; Huiqin Chen; Yun Cai; Pingping Zhang; Zhuanggui Chen

doi:10.18632/oncotarget.17458

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Research Papers:

Association of STAT4 and PTPN22 polymorphisms and their interactions with type-1 autoimmune hepatitis susceptibility in Chinese Han children

Xiaofeng Li, Huiqin Chen, Yun Cai, Pingping Zhang and Zhuanggui Chen _

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Oncotarget. 2017; 8:60933-60940. https://doi.org/10.18632/oncotarget.17458

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Abstract

Xiaofeng Li1, Huiqin Chen1, Yun Cai1, Pingping Zhang1 and Zhuanggui Chen1

1Department of Pediatrics, The Third Affiliated Hospital of Sun Yat-sen University, Guangzhou 510630, China

Correspondence to:

Zhuanggui Chen, email: [email protected]

Keywords: autoimmune hepatitis, STAT4, PTPN22, single nucleotide polymorphism, interaction

Received: February 09, 2017 Accepted: April 12, 2017 Published: April 27, 2017

ABSTRACT

Aims: To investigate the impact of signal transducer and activator of transcription 4 (STAT4) and the protein tyrosine phosphatase N22 (PTPN22) gene single nucleotide polymorphisms (SNPs), gene–gene interactions and haplotype on type-1 Autoimmune Hepatitis (AIH) risk.

Results: Logistic regression analysis showed that type 1 AIH was significantly higher in carriers of T allele of rs7574865 than those with GG genotype (P- value less than 0.001), higher in carriers of C allele of rs7582694 than those with GG genotype (P- value < 0.001), and lower in carriers of T allele of rs2476601 than those with CC genotype (P- value < 0.001). GMDR model indicated a significant two-locus model (p = 0.0100) involving rs7582694 and rs2476601. Participants with GC or CC of rs7582694 and CC of rs2476601 genotype have the highest type 1 AIH risk (P- value < 0.001), after covariates adjustment. Haplotype containing the rs7582694-C and rs7574865-T alleles were associated with a statistically increased type 1 AIH risk (P < 0.001).

Materials and Methods: Logistic regression was performed to investigate association between SNPs within STAT4 and PTPN22 gene and susceptibility to type 1 AIH. Generalized multifactor dimensionality reduction (GMDR) was used to screen the best interaction combinations among the 4 SNPs.

Conclusions: We conclude that rs7574865 and rs7582694 in STAT4 gene minor alleles, interaction between rs7582694 and rs2476601, and haplotype containing the rs7582694-C and rs7574865-T alleles are associated with increased type 1 AIH risk, but rs2476601 in PTPN22 gene minor allele is associated with decreased type 1 AIH risk.

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Research Papers:

Association of STAT4 and PTPN22 polymorphisms and their interactions with type-1 autoimmune hepatitis susceptibility in Chinese Han children

Abstract