Abstract：
The pathogenesis of recurrent pregnancy loss (RPL) is multifactorial and not completely elucidated. Dysregulated immunity was implicated with RPL, in which regulatory T cells (Tregs) are key. As Tregs development and function are regulated by forkhead box P3 (FOXP3) transcription factor, and as FOXP3 expression is genetically determined, a role for FOXP3 polymorphisms in RPL pathogenesis was suggested.
To investigate the association of rs2294021, rs2232365, rs3761548, and rs141704699 FOXP3 variants with idiopathic RPL in Lebanese women.
This retrospective case-control study included 386 RPL cases and 398 age-matched control women. Logistic odds ratios (OR) were estimated with 95% confidence interval after adjustment; a significance value of P<.05 was set.
Significantly lower rs22944021 and rs2232365 minor allele frequency (MAF) was found in patients with idiopathic RPL in comparison with the control group. Furthermore, statistically significantly lower frequency of heterozygous and homozygous rs2294021 and rs2232365 genotypes was seen in controls, while significantly lower rs3761548 heterozygous genotype frequencies were found in the patient group. Obesity, antihypertension treatment, smoking, positive RPL family history, abortion state, and infertility treatment correlated negatively with rs2294021, while rs2232365 negatively correlated with obesity, and rs3761548 negatively correlated with infertility treatment. Marked linkage disequilibrium (LD) was noted among FOXP3 SNPs, with TGCC and CGAC haplotypes being positive, while CAAC, CACC, and TGAC haplotypes being negatively associated with RPL risk. Except for CGAC, the association of these haplotypes with RPL persisted after adjustment.
FOXP3 gene variants and haplotypes are associated with altered incidence of RPL, proposing the role of Treg in RPL pathogenesis.
To investigate the association of rs2294021, rs2232365, rs3761548, and rs141704699 FOXP3 variants with idiopathic RPL in Lebanese women.
This retrospective case-control study included 386 RPL cases and 398 age-matched control women. Logistic odds ratios (OR) were estimated with 95% confidence interval after adjustment; a significance value of P<.05 was set.
Significantly lower rs22944021 and rs2232365 minor allele frequency (MAF) was found in patients with idiopathic RPL in comparison with the control group. Furthermore, statistically significantly lower frequency of heterozygous and homozygous rs2294021 and rs2232365 genotypes was seen in controls, while significantly lower rs3761548 heterozygous genotype frequencies were found in the patient group. Obesity, antihypertension treatment, smoking, positive RPL family history, abortion state, and infertility treatment correlated negatively with rs2294021, while rs2232365 negatively correlated with obesity, and rs3761548 negatively correlated with infertility treatment. Marked linkage disequilibrium (LD) was noted among FOXP3 SNPs, with TGCC and CGAC haplotypes being positive, while CAAC, CACC, and TGAC haplotypes being negatively associated with RPL risk. Except for CGAC, the association of these haplotypes with RPL persisted after adjustment.
FOXP3 gene variants and haplotypes are associated with altered incidence of RPL, proposing the role of Treg in RPL pathogenesis.
摘要：
复发性妊娠丢失（RPL）的发病机理是多因素的，尚未完全阐明。免疫失调与RPL有关，其中调节性T细胞(Tregs)是关键。由于Tregs的发育和功能受到叉头盒P3（FOXP3）转录因子的调控，由于FOXP3的表达是由基因决定的，提示FOXP3多态性在RPL发病机制中的作用.
研究rs2294021、rs2232365、rs3761548和rs141704699FOXP3变异与黎巴嫩女性特发性RPL的关系。
这项回顾性病例对照研究包括386例RPL病例和398例年龄匹配的对照妇女。调整后，用95%置信区间估计Logistic比值比（OR）；设置P<0.05的显著性值。
与对照组相比，特发性RPL患者的rs22944021和rs222365次要等位基因频率（MAF）显着降低。此外，在对照组中观察到杂合和纯合rs2294021和rs222365基因型的统计学显着降低的频率，而显着较低的rs3761548杂合基因型频率在患者组中发现。肥胖,抗高血压治疗,吸烟,RPL家族史阳性,堕胎状态,和不孕症治疗与rs2294021负相关，而rs222365与肥胖负相关，rs3761548与不孕症治疗呈负相关。在FOXP3SNP中注意到标记的连锁不平衡(LD)，TGCC和CGAC单倍型为阳性，而中国民航,CACC,TGAC单倍型与RPL风险呈负相关。除了CGAC,这些单倍型与RPL的关联在调整后仍然存在.
FOXP3基因变异体和单倍型与RPL发生率的改变有关,提示Treg在RPL发病机制中的作用。
研究rs2294021、rs2232365、rs3761548和rs141704699FOXP3变异与黎巴嫩女性特发性RPL的关系。
这项回顾性病例对照研究包括386例RPL病例和398例年龄匹配的对照妇女。调整后，用95%置信区间估计Logistic比值比（OR）；设置P<0.05的显著性值。
与对照组相比，特发性RPL患者的rs22944021和rs222365次要等位基因频率（MAF）显着降低。此外，在对照组中观察到杂合和纯合rs2294021和rs222365基因型的统计学显着降低的频率，而显着较低的rs3761548杂合基因型频率在患者组中发现。肥胖,抗高血压治疗,吸烟,RPL家族史阳性,堕胎状态,和不孕症治疗与rs2294021负相关，而rs222365与肥胖负相关，rs3761548与不孕症治疗呈负相关。在FOXP3SNP中注意到标记的连锁不平衡(LD)，TGCC和CGAC单倍型为阳性，而中国民航,CACC,TGAC单倍型与RPL风险呈负相关。除了CGAC,这些单倍型与RPL的关联在调整后仍然存在.
FOXP3基因变异体和单倍型与RPL发生率的改变有关,提示Treg在RPL发病机制中的作用。
