Association between lower frequency of R381Q variant (rs11209026) in IL-23 receptor gene and increased risk of recurrent spontaneous abortion (RSA)

Abstract

Recurrent spontaneous abortion (RSA) is defined as three or more consecutive spontaneous abortions before the 20th week of gestation. The purpose of the present study was to investigate the association between a functional single nucleotide polymorphism (SNP) in the interleukin (IL)-23 receptor gene (IL-23R; rs11209026, 1142 G wild type ! A reduced function, Arg381Gln, R381Q) and RSA. For the study, 200 RSA patients (confirmed using established diagnostic criteria) and 200 normal individuals in fertility and infertility centers in the cities of Yazd and Isfahan were recruited during a period from 2012-2013. Using PCR-RFLP, the R381Q variant was screened for in the IL-23R gene of the patients and controls. The results indicated there were significant differences in the frequency of this genetic variant in the patients versus the healthy controls, i.e. 2% and 7.5%, respectively (p value ¼ 0.01; odds ratio ¼ 0.25; CI ¼ 95%). No significant difference was found for the G allelic frequency in patients with RSA and in the control group (p ¼ 0.60). The A allelic frequency was significantly different between the two groups (p ¼ 0.01). Based on these findings, it is concluded that the frequency of single nucleotide polymorphism in the IL-23 receptor (R381Q) in patients with recurrent spontaneous abortion (RSA) is less than that found in normal control women.

Protective role of R381Q (rs11209026) polymorphism in IL-23R gene in immune-mediated diseases: A comprehensive review

“…The proportions of T H 17 (CD4 + IL-17A + ) cells in the peripheral blood and decidua were found to be significantly higher in unexplained RSA subjects than in normal pregnant women (Tavasolian et al 2014). The pro-inflammatory features of IL-23 have been linked with T H 17 cell responses through the expansion and maintenance of T H 17 cells (Abdollahi et al 2015). In that study, the association between R381Q variant and recurrent spontaneous abortion was investigated and a significant difference was found between the case and control group subjects with regard to a presence of the R381Q variant.…”

“…Abdollahi et al (2015) reported that the number and activity of both circulating T H 17 cells and in vitro (ex vivo)-differentiated T H 17 cells did not differ between G and A allele carriers. This finding supported the belief for a major role for IL-23 in generation of T H 17 cell effector responses during tissue inflammation (rather than in systemic inflammation) and demonstrated the importance of IL-23 in mediating T H 17 effector responses in humans.…”

“…IL-17A production, rather than of T H 17 cell differentiation (Mosayebian et al 2015). The R381Q allele conferred protection against IBD (including CD and UC) (Duerr et al 2006), psoriasis (Capon et al 2007), ankylosing spondylitis (Rueda et al 2008), Graft-vs-Host (GVH) disease after marrow transplantation (Elmaagacli et al 2008), rheumatoid arthritis, recurrent spontaneous abortion (RSA) or asthma (Abdollahi et al 2015;Mosayebian et al 2015).…”

Altered Expression of MicroRNAs in Rheumatoid Arthritis

“…In humans, Th17 cells can be induced by IL-6, IL-1b, and TNF-a, which are abundant in the inflamed joint of patients with active disease, and are directly involved in cartilage and bone destruction. Therefore, IL-17 is described as an inflammatory cytokine which has a role in many inflammatory conditions [Abdollahi et al, 2015[Abdollahi et al, , 2016.…”

Association of 14-bp insertion/deletion polymorphism of HLA-G gene with idiopathic recurrent miscarriages in infertility center patients in Yazd, Iran

“…Recurrent miscarriage (RM), defined as the loss of three or more consecutive pregnancies in the first trimester of pregnancy, affects $1-2% of fertile women (Abdollahi et al, 2014;Matter & Sharif, 2013). At present, there are some accepted etiologies for RM (Ford & Schust, 2009) (Figure 1), including parental chromosomal abnormalities, untreated hypo-thyroidism, uncontrolled diabetes mellitus, certain uterine anatomic abnormalities and anti-phospholipid antibody syndrome (APS), endocrine disorders, heritable/acquired thrombophilias, immunologic abnormalities, infections and environmental factors.…”