TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility

Abstract

Introduction: Tyrosine kinase 2 gene (TYK2) is part of the janus kinase (JAK) that binds to the type I interferon-α receptor (IFNAR) on the cell surface of IFN-producing cells, and have crucial importance in the etiology of autoimmune and inflammatory diseasesMany polymorphisms of the TYK2 gene have been identified, and recently, a number of case-control studies were conducted to investigate the association of these polymorphisms with autoimmune and inflammatory diseases, with conflicting resultsBased on these observations, we hypothesized that the TYK2 polymorphisms (rs34536443, rs2304256, rs280523, rs12720270 and rs12720356) might be involved in the pathogenesis of endometriosis and/or infertility Methods: Genetic association study comprising 275 infertile women with endometriosis, 92 women with idiopathic infertility and 307 fertile women as controlsTYK2 polymorphisms were identified by TaqMan PCRGenotype distribution, allele frequency and haplotype analysis of the TYK2 polymorphisms were performedA p-value <0.05 was considered significant Results: Single-marker analysis revealed that TYK2 rs34536443 was significantly associated with protection against endometriosis-related infertility, especially in moderate/severe disease (p=0.002; OR=0.24, 95% IC=0.09-0.62)No difference was found considering the infertile group without endometriosisNo associations were found considering rs2304256, rs280523, rs12720270 and rs12720356 either for endometriosis-related infertility group or idiopathic infertility groupHaplotype analysis of five TYK2 polymorphisms identified a haplotype "CTATG" associated with protection against endometriosis-related infertility, especially in moderate/severe disease (p=0.027) Conclusion: This is the first study to report an association between TYK2 polymorphisms and endometriosis and/or infertilityThese findings require replication in other populations but suggest the TYK2 rs34536443 polymorphisms and "CTATG" haplotype can be associated with a decreased susceptibility to endometriosis-related infertility in Brazilian women. © 2012 American Society for Histocompatibility and Immunogenetics.