Laboratory of Human Genome and Multifactorial Diseases (LR12ES07), University of Monastir, Monastir, Tunisia.
Faculty of Science of Bizerte, University of Carthage, Tunis, Tunisia.
BJOG. 2018 May;125(6):729-735. doi: 10.1111/1471-0528.14949. Epub 2017 Nov 13.
To investigate the association of progesterone receptor (PGR) gene variants with susceptibility to recurrent pregnancy loss (RPL).
Retrospective case-control study.
Outpatient obstetrics and gynaecology clinics.
Women with RPL (396), defined as three or more consecutive miscarriages of unknown aetiology, and 361 women used as controls.
PGR genotyping was performed by the allelic exclusion method (real-time polymerase chain reaction).
PGR single nucleotide polymorphisms (SNPs) and the distribution of their alleles, genotypes and haplotypes.
Higher minor allele frequencies (MAFs) for rs590688, rs10895068, and rs1942836 were seen in RPL cases than in controls, which remained significant after controlling for multiple comparisons. Significantly higher frequencies of heterozygous (1/2) rs608995, along with heterozygous (1/2) and homozygous (2/2) rs590688, rs10895068, and rs1942836 genotype carriers, were seen between RPL cases versus controls, respectively, which persisted after controlling for age, body mass index (BMI), and menarche. The increased risk of RPL associated with rs590688 and rs1942836 was dependent on the number of minor alleles, thus suggesting a 'dose-dependent' effect associated with both variants. Varied linkage disequilibrium (LD) was noted between rs590688, rs10895068, rs608995, and rs1942836 PGR variants associated with RPL. Haplotypes with an increased frequency of CGTC and reduced frequency of GGAT were noted in women with RPL, compared with controls, thereby indicating these haplotypes as RPL-susceptible and RPL-protective, respectively. This association persisted after controlling for multiple comparisons, and after adjusting for covariates.
We have confirmed a positive association of specific PGR variants (rs590688, rs10895068, and rs1942836) and PGR haplotypes (ATGCCGTC and ATTCGGTC) with an increased risk of RPL, thereby supporting a role for PGR as an RPL candidate locus.
Genetic variants in progesterone receptor gene are associated with increased risk of recurrent pregnancy loss.
探讨孕激素受体（PGR）基因变异与复发性妊娠丢失（RPL）易感性的关系。
回顾性病例对照研究。
门诊妇产科诊所。
RPL 患者（396 例），定义为三次或三次以上不明原因的连续流产，以及 361 例作为对照的女性。
采用等位基因排除法（实时聚合酶链反应）进行 PGR 基因分型。
PGR 单核苷酸多态性（SNP）及其等位基因、基因型和单倍型的分布。
与对照组相比，RPL 病例中 rs590688、rs10895068 和 rs1942836 的次要等位基因频率（MAF）更高，经多重比较校正后仍有统计学意义。rs608995 的杂合子（1/2）、rs590688、rs10895068 和 rs1942836 的杂合子（1/2）和纯合子（2/2）基因型携带者在 RPL 病例与对照组之间的频率均较高，校正年龄、体重指数（BMI）和初潮后仍有统计学意义。与 rs590688 和 rs1942836 相关的 RPL 风险增加与少数等位基因的数量有关，因此提示与这两种变异均存在“剂量依赖性”效应。rs590688、rs10895068、rs608995 和 rs1942836PGR 变异与 RPL 相关，其连锁不平衡（LD）存在差异。与对照组相比，RPL 患者的 CGTC 频率增加，GGAT 频率降低的单倍型更为常见，表明这些单倍型分别为 RPL 易感和 RPL 保护。校正多重比较和协变量后，这种关联仍然存在。
我们已经证实，特定的 PGR 变异（rs590688、rs10895068 和 rs1942836）和 PGR 单倍型（ATGCCGTC 和 ATTCGGTC）与 RPL 风险增加之间存在正相关，从而支持 PGR 作为 RPL 候选基因座的作用。
孕激素受体基因的遗传变异与复发性妊娠丢失的风险增加有关。
