title: Contribution of JAK2 and STAT3 variants to the genetic susceptibility of recurrent spontaneous miscarriage in a Tunisian population.
abstract: OBJECTIVE
  Th1 and Th2 balance is crucial for maintenance of pregnancy, and intracellular JAK and STAT proteins significantly contribute to it. In view of evidence linking JAK2 and STAT3 variants with recurrent spontaneous miscarriage (RSM), here we investigated the association of JAK2 (rs2230724) and STAT3 (rs1053023 and rs1053004) to RSM susceptibility in Tunisians.
  
  
  METHODS
  A retrospective case-control study. Subjects comprised 235 RSM cases and 235 control subjects. JAK2 and STAT3 were genotyped by the allelic discrimination method.
  
  
  RESULTS
  STAT3 rs1053023 and, to a lower extent, rs1053004 were significantly associated with RSM under the additive and dominant, but not recessive models. This remained significant after adjustment for the covariates age, smoking, and gravida. In contrast to STAT3 variants, JAK2 rs2230724 was not associated with RSM under any of the genetic models tested. Two-locus STAT3 (rs1053023/rs1053004) haplotype analysis revealed increased frequency of the C/G haplotype in patients with RSM. Multivariate regression analysis confirmed the association of C/G haplotype with RSM (p=0.001; odds ratio=2.01; 95% confidence interval=1.32-3.07), thus conferring RSM susceptibility nature. These differences remained significant after applying the Bonferroni correction for multiple testing (Pc=0.004).
  
  
  CONCLUSIONS
  STAT3 rs1053023, more so than the STAT3 rs1053004 or JAK2 rs2230724 polymorphisms, is associated with RSM risk.
authors.affiliation: Research Unit of Biology and Genetics of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia. safsafsophie@gmail.com
authors.forename: Safia
authors.initials: S
authors.lastname: Messaoudi
authors.forename: Sondes
authors.initials: S
authors.lastname: Hizem
authors.forename: Manar A
authors.initials: MA
authors.lastname: Al-Sulaiti
authors.forename: Amna S
authors.initials: AS
authors.lastname: Al-Busaidi
authors.forename: Kalthoum
authors.initials: K
authors.lastname: Magdoud
authors.forename: Maryam
authors.initials: M
authors.lastname: Dendana
authors.forename: Wassim Y
authors.initials: WY
authors.lastname: Almawi
authors.forename: Touhami
authors.initials: T
authors.lastname: Mahjoub
mesh_terms: D000026:Abortion, Habitual / Q000208:ethnology / Q000235:genetics*; D000328:Adult; D016022:Case-Control Studies; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D014644:Genetic Variation; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D053614:Janus Kinase 2 / Q000235:genetics*; D015999:Multivariate Analysis; D011247:Pregnancy; D012189:Retrospective Studies; D050796:STAT3 Transcription Factor / Q000235:genetics*; D014416:Tunisia
chemical_list: D050796:STAT3 Transcription Factor; C494086:STAT3 protein, human; C507924:JAK2 protein, human; D053614:Janus Kinase 2