Contribution of JAK2 and STAT3 variants to the genetic susceptibility of recurrent miscarriage among Bahraini and Tunisian Arabs

Abstract

We investigated the contribution of JAK2 rs2203724 and STAT3 rs1053023 and rs1053004 to the susceptibility of idiopathic recurrent miscarriage (IRM) in Bahraini (246 cases and 279 controls) and Tunisian (235 cases and 235 controls) Arabs. The distribution of JAK2 rs2203724 and STAT3 rs1053023 genotypes were in Hardy-Weinberg equilibrium (HWE) in both communities, while mild deviation from HWE was noted for rs1053004 in Tunisians but not Bahraini. JAK2 rs2203724 was not associated with IRM in either community, while STAT3 rs1053023 was positively associated with IRM in both Bahraini and Tunisian women. STAT3 rs1053004 displayed mixed association: it was positively associated with IRM in Bahraini (P < 0.001), but not Tunisian women (P = 0.10). Genotype association confirmed the association of both STAT3 variants with IRM under additive, dominant, and recessive models, while the association of STAT3 rs1053023 was seen under additive and dominant, but not recessive models in Tunisians. The contribution of JAK2 and STAT3 variants to IRM susceptibility must be evaluated regarding specific variants, and the ethnic/racial background.

Association of Single Nucleotide Polymorphism rs1053004 in Signal Transducer and Activator of Transcription 3 (STAT3) with Susceptibility to Hepatocellular Carcinoma in Thai Patients with Chronic Hepatitis B

“…These findings were consistent with the data conducted in the recent Chinese cohort (T allele: 65.63% and C allele: 34.37%) (Xie et al, 2013), suggesting that the SNP has homogeneity in the allele distribution among East-Asian (Thai and Chinese) populations. Interestingly, in contrast to our report, the frequency of C allele was higher than T allele in Tunisian Arabs (Middle East) (Messaoudi et al, 2013a;2013b). SNP rs1053004, localized on 3'-UTR of STAT3, regulates expression of STAT3 protein by altering mRNA degradation and decreased STAT3 activity (Foshay and Gallicano, 2009;Xie et al, 2013).…”

Impact of miRNA-binding site polymorphisms in STAT3 gene on occurrence and clinical characteristics of systemic lupus erythematosus

“…43 Besides, Messaoudi et al, reported that the G allele in rs1053023 polymorphism is associated with recurrent miscarriages in Bahraini and Tunisian Arab populations. 44,45 This result was not surprising, as previous studies revealed higher levels of p-STAT3, IL17, and IL17R in patients with unexplained recurrent spontaneous abortions. 46,47 In another study evaluating the association between these two polymorphisms in STAT3 and the risk of developing noise-induced hearing loss (NIHL), it was demonstrated that the G allele in both variants was linked with NIHL risk.…”

Genetic Association between Inflammatory-Related Polymorphism in STAT3, IL-1β, IL-6, TNF-α and Idiopathic Recurrent Implantation Failure

“…Additionally, the IL-1 family is well-known to be involved in inflammation; specifically, the role of IL-1β in relation to the development of inflammatory diseases is well established [ 34 ]. Moreover, studies of the STAT3 rs1053004, IL-6 rs1800796, and TNF-α rs1800629 polymorphisms suggested their significant association with recurrent miscarriage as well as abnormal inflammation responses [ 6 , 35 , 36 , 37 , 38 , 39 ]. Specifically, the IL-6 rs1800796 G and TNF-α rs1800629 A alleles have significant associations with an increased risk of pregnancy complications [ 40 , 41 ].…”