Gene-gene and gene-sex epistatic interactions of DNMT1, DNMT3A and DNMT3B in autoimmune thyroid disease

Endocrine Journal

Jian Xu²  Jian Zhang¹  Rong-hua Song²  Xuan Wang²  Qiu Qin²  Jiao-zhen Zhou²  Jin-an Zhang²  Tian-tian Cai²  Fatuma-said Muhali² 

[1] Clinical Laboratory, Jinshan Hospital of Fudan University, Shanghai 201508, China;Department of Endocrinology, Jinshan Hospital of Fudan University, Shanghai 201508, China

关键词: DNA methyltransferases (DNMTs);    Autoimmune thyroid diseases;    Graves’ disease;    Hashimoto’s thyroiditis;    Single nucleotide polymorphism (SNP);   

DOI  :  10.1507/endocrj.EJ15-0596

学科分类：内分泌与代谢学

来源: Japan Endocrine Society

【 摘 要 】

References(42)The aim of this study was to investigate the associations of DNA methyltransferases (DNMTs) polymorphisms with susceptibility to autoimmune thyroid diseases (AITDs) and to test gene-gene/gene-sex epistasis interactions.Eight single-nucleotide polymorphisms (SNPs) in DNMT1, DNMT3A and DNMT3B were selected and genotyped by multiplex polymerase chain reaction combined with ligase detection reaction method (PCR-LDR).A total of 685 Graves’ disease (GD) patients, 353 Hashimoto’s thyroiditis (HT) patients and 909 healthy controls were included in the final analysis.Epistasis was tested by additive model, multiplicative model and general multifactor dimensionality reduction (general MDR).Rs2424913 (DNMT3B) and rs2228611 (DNMT1) were associated with susceptibility to AITD and GD in the dominant and overdominant model, respectively (rs2424913: P=0.009 for AITD, P=0.0041 for GD; rs2228611: P=0.035 for AITD, P=0.043 for GD).Multiplicative and multiple high dimensional gene-gene or gene-sex interactions were also observed in this study.We have found evidence for a potential role of rs2424913 (DNMT3B) and rs2228611 (DNMT1) in AITD susceptibility and identified novel gene-gene/gene-sex interactions in AITD.Our study may highlight sex and genes of DNMTs family as contributors to the pathogenesis of AITD.

【 授权许可】

Unknown