A rare variant in the IL22RA2 gene is associated with unexplained recurrent pregnancy loss in Han Chinese women

Introduction Recurrent pregnancy loss (RPL) occurred in ~1-2% of reproductive women. Previous studies have implicated that altered expression and polymorphisms of interleukin-related genes might be involved in RPL. The aim of this study was to explore the potential presence of interleukin-22 receptor subunit alpha-2 (IL22RA2) mutations in Han Chinese women with unexplained recurrent pregnancy loss (URPL). Material and methods A total of 328 Han Chinese women with URPL were analyzed for the potential mutations in the IL22RA2 gene by sequencing all of the exons. Furthermore, 615 Han Chinese control women without miscarriage history were also analyzed. Evolutionary conservation and in silico analyses were performed to predict the potential pathogenicity of IL22RA2 mutations. Results A rare variant, p.Arg204* (c.610C>T), was identified in 4 out of 328 URPL samples. In contrast, this rare variant was absent in 615 Han Chinese control women without miscarriage history and had a significantly higher mutation frequency when compared with 10588 Chinese control samples from The China Metabolic Analytics Project (ChinaMAP), 4245 East Asians, or 60051 individuals across the world from the Exome Aggregation Consortium (ExAC) database. Evolutionary conservation analysis indicated this rare variant was highly conserved from Human to Zebrafish, in silico analysis implicated this rare variant might be pathogenic. Conclusions An enrichment of a potentially pathogenic rare variant in the IL22RA2 gene was observed in URPL patients, for the first time, implicating this rare variant might be associated with the development of URPL. However, further functional assays would be performed to confirm the potential role of this rare variant in URPL.