Association of the IL-10 receptor A536G (S138G) loss-of-function variant with recurrent miscarriage.

We investigated the association of interleukin-10 receptor (IL10R1) loss-of-function variant A536G/S138G with recurrent pregnancy loss (RPL). Study subjects comprised 300 women with ≥3 miscarriages, and 350 control women. Significantly higher 536G-allele frequency was seen in RPL cases, thus assigning pathogenic role for this allele. Significant difference in A536G/S138G genotypes distribution was seen between RPL cases and controls, evidenced by enrichment of 536A/G and 536G/G genotypes in RPL cases. Setting A/A genotype as reference (OR = 1.00), increased RPL risk was seen with 536A/G, and more in 536G/G carriers, thereby establishing dose-dependency. IL10R1 loss-of-function A536/S138G polymorphism may contribute to RPL pathogenesis.