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The current study was aimed to investigate the association of CLTA-4/Foxp3 polymorphisms and chromosomal abnormalities with recurrent spontaneous abortion (RSA) risk in a Chinese Han population. Altogether, 1284 RSA women and 1046 women with normal pregnancy were incorporated in this study. The polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) was implemented to genotype the single-nucleotide polymorphisms (SNPs) located within CTLA4 and Foxp3. Moreover, the cytogenetic diagnosis was performed in line with the standards of G banding karyotype. As a consequence, rs231775 and rs3087243 of CTLA4, as well as rs2232365 and rs2232368 of Foxp3, all appeared to modify the risk of RSA. Besides, significant differences were found between the ratio of structural abnormality and that of numerical abnormality (P &lt; 0.038), and chromosome abnormality was associated with higher miscarriage frequency (&gt;3) than normal karyotypes. Of note, the synergic effects of the genotypes and chromosomal abnormality all tallied with the sub-multiplication model (OR chromosome  × OR SNP  &gt; OR chromosome+SNP ), while rs2232365 GG and chromosomal aberration impacted the RSA risk in a super-multiplicative way that OR chromosome  × OR SNP  &lt; OR chromosome+SNP . In conclusion, susceptibility to RSA was subject to the synthetic regulation of chromosomal aberrations and genetic mutations within CLTA-4 and Foxp3, suggesting that the conduction of karyotype analysis and genetic detection for RSA patients could effectively guide effective RSA counseling and sound child rearing.

journal of human genetics

The synergic effects of CTLA-4/Foxp3-related genotypes and chromosomal aberrations on the risk of recurrent spontaneous abortion among a Chinese Han population