Study on association of functional polymorphisms in Foxp3 gene with the susceptibility to unexplained recurrent spontaneous abortion

Abstract

To investigate the association between the functional polymorphisms of Foxp3 gene and unexplained recurrent spontaneous abortion (URSA). PCR-restriction fragment length polymorphism (rs3761548, rs2294021) and PCR with sequence-specific primers (rs2232365, rs5902434) were used to detect four polymorphisms of Foxp3 in 146 URSA cases and 112 normal controls. (1) The frequencies of rs3761548A/C were 10.3%, 22.3% in genotype C/C, 38.4%, 40.2% in genotype A/C and 51.4%, 37.5% in genotype A/A between URSA patients and normal controls; the frequencies of rs2232365A/G were 5.5%, 15.2% in genotype A/A, 47.9%, 50.0% in genotype A/G, 46.6%, 34.8% in genotype G/G between URSA patients and normal controls; they all reached statistical difference (P < 0.05). The carriers of rs3761548A allele and rs2232365G allele increased the risk of URSA (OR = 1.73, 1.61;all P < 0.05). (2) There was no difference in the genotypic distribution of rs5902434del/ATT polymorphism between cases and controls (P = 0.10), but the frequency of del allele in URSA was statistically increased than that of controls (71.2%, 62.5%;OR = 1.49, P = 0.04). (3) There was no different distribution in 3 genotypes (C/C, T/C, T/T) and 2 alleles (T and C) of rs2294021T/C between URSA patients and normal controls (P = 0.18 and 0.08). (4) Estimated haplotype frequency distribution of rs5902434del/ATT, rs3761548A/C and rs22323565A/G showed haplotype del-A-G conferring the susceptibility to URSA (OR = 2.51, P < 0.01) but haplotype del-C-G and ATT-A-A could provide protection on URSA (OR = 0.18, 0.22; all P < 0.01). Functional polymorphisms of Foxp3 gene could probably confer the susceptibility to URSA, by altering Foxp3 function and (or) its expression.