Association of Human forkhead box protein 3 (FOXP3) gene polymorphisms with idiopathic recurrent pregnancy loss among Kazakhstani women
2021
Recurrent pregnancy loss (RPL) is major pregnancy complication, with poorly defined cause.Forkhead Box P3 (FOXP3) is a transcription factor that supports Treg activation and development and attenuates immune responses. As FOXP3 production is genetically determined, we tested the association of FOXP3 gene variants with RPL.A retrospective case-control study, performed between April 2019 and February 2020. Study subjects comprised 62 RPL cases and 60 control women. Genotyping of the four FOXP3 variants rs2294021 (T > C), rs2232365 (G > A), rs3761548 (C > A), and rs141704699 (C > T) was done by real-time PCR, with defined clusters. Logistic odds ratios (ORs) of RPL risk were estimated with 95% confidence interval (CI) after adjustment; statistical significance set at P < 0.05.Minor allele frequency (MAF) of rs2294021 was significantly lower [P < 0.001; OR(95% CI) = 0.25(0.11–0.55)], while rs2232365 MAF was significantly higher [P = 0.045; OR(95% CI) = 1.85(1.05–3.28)] in cases, hence assigning RPL-protection and -susceptibility to these variants, respectively. Increased RPL risk was seen in rs2232365 homozygous minor allele carrying genotype [OR(95% CI) = 5.14(1.01–26.15)], while reduced RPL risk was noted in rs2294021 heterozygous [OR(95% CI) = 0.30(0.11–0.80)], and homozygous minor allele [OR(95% CI) = 0.10(0.01–0.83)] genotype carriers. Moderate linkage disequilibrium analysis was seen between the tested variants. Increased frequency of TACC, and reduced frequency of CGAC haplotypes were seen in RPL cases when compared to controls, thereby assigning RPL susceptibility and protection to these haplotypes, respectively.These results suggest that FOXP3 variants and haplotypes are associated with idiopathic RPL, suggesting the likely contribution of Treg to RPL.
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