title: TYK2 rs34536443 polymorphism is associated with a decreased susceptibility to endometriosis-related infertility.
abstract: BACKGROUND
  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 diseases. Many 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 results. Based 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 controls. TYK2 polymorphisms were identified by TaqMan PCR. Genotype distribution, allele frequency and haplotype analysis of the TYK2 polymorphisms were performed. A 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 endometriosis. No associations were found considering rs2304256, rs280523, rs12720270 and rs12720356 either for endometriosis-related infertility group or idiopathic infertility group. Haplotype analysis of five TYK2 polymorphisms identified a haplotype "CTATG" associated with protection against endometriosis-related infertility, especially in moderate/severe disease (p = 0.027).
  
  
  CONCLUSIONS
  This is the first study to report an association between TYK2 polymorphisms and endometriosis and/or infertility. These 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.
authors.affiliation: Human Reproduction and Genetics Center, Department of Gynecology and Obstetrics, Faculdade de Medicina do Santo Andre, Sao Bernardo do Campo and Sao Caetano do Sul County, Santo Andre, Brazil.
authors.forename: Carla
authors.initials: C
authors.lastname: Peluso
authors.forename: Denise M
authors.initials: DM
authors.lastname: Christofolini
authors.forename: Cecília S
authors.initials: CS
authors.lastname: Goldman
authors.forename: Fernanda A
authors.initials: FA
authors.lastname: Mafra
authors.forename: Viviane
authors.initials: V
authors.lastname: Cavalcanti
authors.forename: Caio P
authors.initials: CP
authors.lastname: Barbosa
authors.forename: Bianca
authors.initials: B
authors.lastname: Bianco
mesh_terms: D000328:Adult; D000483:Alleles; D001938:Brazil; D016022:Case-Control Studies; D004715:Endometriosis / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D007247:Infertility, Female / Q000235:genetics* / Q000473:pathology; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D053634:TYK2 Kinase / Q000235:genetics*
chemical_list: D053634:TYK2 Kinase; C070139:TYK2 protein, human