TP63基因与MDM2基因之间的相互作用及复发性流产风险

Interaction between TP63 and MDM2 genes and the risk of recurrent pregnancy loss.

作者信息

Fraga Lucas R, Boquett Juliano A, Dutra Caroline G, Vianna Fernanda S, Heck Camila, Gonçalves Rozana O, Paskulin Diego D, Costa Olívia L, Ashton-Prolla Patrícia, Sanseverino Maria Teresa V, Schuler-Faccini Lavínia

机构信息

Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil.

Post-Graduation Program in Genetics and Molecular Biology, Department of Genetics, Biosciences Institute, Universidade Federal do Rio Grande do Sul (UFRGS), Porto Alegre 91501-970, Brazil; INAGEMP - Instituto Nacional de Genética Médica Populacional, Universidade Federal do Rio Grande do Sul, Porto Alegre 91501-970, Brazil; Postgraduate Program in Epidemiology. Universidade Federaldo Rio Grande do Sul, Porto Alegre, Rio Grande do Sul, Brazil.

出版信息

Eur J Obstet Gynecol Reprod Biol. 2014 Nov;182:7-10. doi: 10.1016/j.ejogrb.2014.07.044. Epub 2014 Aug 24.

DOI:10.1016/j.ejogrb.2014.07.044

PMID:25218545

Abstract

OBJECTIVE

Recent studies have investigated the role of the p53 gene family in reproductive processes. Each member of the gene family acts through different mechanisms: p53 is involved in genomic stability and regulation of blastocyst implantation; p63 acts as a regulator of the quality and maturation of oocytes; and p73 controls the meiotic spindle. Polymorphisms in the genes of the p53 family have been associated with female infertility. One polymorphism in MDM2, the main regulator of the p53 family, has also been associated with this condition. Although polymorphisms in the TP53 gene have been related to recurrent pregnancy loss (RPL), there have been no studies associating polymorphisms in p63 and p73 with RPL. Therefore, the aim of this study was to evaluate the role of polymorphisms in the TP63 (rs17506395), TP73 (rs2273953, rs1801173), and MDM2 (SNP309, rs2279744) genes as risk factors for RPL.

STUDY DESIGN

A case-control study was conducted in 153 women with RPL and 143 fertile women with at least two living children and no history of pregnancy loss. Molecular analysis was performed by TaqMan Allelic Discrimination assay. The statistical analysis was performed using SPSS software version 20.0 and the chi-square test, Student's t-test, Mann-Whitney test and logistic regression to compare the evaluated characteristics between both groups and RPL outcome.

RESULTS

The allelic and genotypic frequencies did not differ between the groups when analyzed separately, however, the interaction between the TP63 TT and MDM2 TT genotypes was shown to increase the risk of RPL (OR=2.19, CI 95%: 1.28-3.75, p=0.004), even when adjusted for alcohol consumption, smoking, number of pregnancies and ethnicity (OR=1.97, CI 95%: 1.27-3.58, p=0.025).

CONCLUSIONS

Our results suggest that genes from the p53 family proteins, evaluated here, have an influence on the risk of RPL.

摘要

目的

近期研究探讨了p53基因家族在生殖过程中的作用。该基因家族的每个成员通过不同机制发挥作用：p53参与基因组稳定性和胚泡着床调控；p63作为卵母细胞质量和成熟的调节因子；p73控制减数分裂纺锤体。p53家族基因多态性与女性不孕有关。p53家族的主要调节因子MDM2中的一种多态性也与这种情况相关。虽然TP53基因多态性与复发性流产（RPL）有关，但尚无研究将p63和p73基因多态性与RPL联系起来。因此，本研究旨在评估TP63（rs17506395）、TP73（rs2273953、rs1801173）和MDM2（SNP（单核苷酸多态性）309、rs2279744）基因多态性作为RPL危险因素的作用。

研究设计

对153例复发性流产女性和143例至少有两个存活子女且无流产史的可育女性进行病例对照研究。采用TaqMan等位基因鉴别分析进行分子分析。使用SPSS 20.0软件进行统计分析，并采用卡方检验、学生t检验、曼-惠特尼检验和逻辑回归来比较两组之间评估的特征及RPL结局。

结果

单独分析时，两组之间的等位基因和基因型频率没有差异，然而，TP63基因TT基因型与MDM2基因TT基因型之间的相互作用显示会增加RPL风险（比值比（OR）=2.19，95%置信区间（CI）：1.28 - 3.75，p = 0.004）；即使在对饮酒、吸烟、妊娠次数和种族进行校正后（OR = 1.97，95%CI：1.27 - 3.58，p = 0.025），依然如此。