Stavros Sofoklis, Mavrogianni Despoina, Papamentzelopoulou Myrto, Basamakis Evaggelos, Khudeir Hend, Psarris Alexandros, Drakakis Peter
1st Department of Obstetrics and Gynecology 'Alexandra' General Hospital, Molecular Biology Unit, Division of Human Reproduction and Recurrent Abortions, National and Kapodistrian University of Athens, 80, Vasilissis Sofias Ave., 11528, Athens, Greece.
Fertil Res Pract. 2021 Apr 10;7(1):9. doi: 10.1186/s40738-021-00101-x.
Promoter region SNPs in TNF-α have been studied in association with Recurrent Pregnancy Loss (RPL) occurrence in various populations. Among them, -238G > A, -308G > A and - 376G > A have been frequently investigated for their potential role in recurrent abortions. The aim of the present study is to evaluate the correlation among TNF-α 238, TNF-α 308 and TNF-α 376 polymorphisms and recurrent pregnancy loss risk in Greek women.
This study included 94 Caucasian women with at least two miscarriages of unexplained aetiology, before the 20th week of gestation. The control group consisted of 89 Caucasian women of proven fertility, with no history of pregnancy loss. DNA samples were subjected to PCR amplification using specific primers. Sanger sequencing was applied to investigate the presence of TNF-α 238, TNF-α 308, TNF-α 376 polymorphisms in all samples.
The TNF-α 238 and TNF-α 308 variants were both detected in RPL and control groups (7.45% vs 4.49 and 45.16% vs 36.73%, respectively), but with no statistically significant association (p-value 0.396 and 0.374, respectively). The TNF-α 376 variant was not detected at all in both control and RPL groups. When TNF-α 238 and TNF-α 308 genotypes were combined no association with RPL was detected (p-value = 0.694). In subgroup analysis by parity, RPL patients carrying the A allele reported less previous births.
This is the first study demonstrating TNF-α 238 and TNF-α 308 gene expression and the absence of TNF-α 376 variant in Greek women with RPL. However, no association emerged between each polymorphism studied and the occurrence of recurrent pregnancy loss. Accordingly, TNF-α -308G > A, -238G > A and -376G > A variants are not considered genetic markers for identifying women at increased risk of recurrent pregnancy loss in the Greek population.
肿瘤坏死因子-α（TNF-α）启动子区域单核苷酸多态性（SNP）已在不同人群中与复发性流产（RPL）的发生相关联进行了研究。其中，-238G>A、-308G>A和-376G>A因其在复发性流产中的潜在作用而受到频繁研究。本研究的目的是评估希腊女性中TNF-α 238、TNF-α 308和TNF-α 376多态性与复发性流产风险之间的相关性。
本研究纳入了94名在妊娠20周前有至少两次不明原因流产的白种女性。对照组由89名已证实有生育能力且无流产史的白种女性组成。使用特异性引物对DNA样本进行PCR扩增。应用桑格测序法检测所有样本中TNF-α 238、TNF-α 308、TNF-α 376多态性的存在情况。
在RPL组和对照组中均检测到了TNF-α 238和TNF-α 308变体（分别为7.45%对4.49%和45.16%对36.73%），但无统计学显著关联（p值分别为0.396和0.374）。在对照组和RPL组中均未检测到TNF-α 376变体。当将TNF-α 238和TNF-α 308基因型合并时，未检测到与RPL的关联（p值=0.694）。在按产次进行的亚组分析中，携带A等位基因的RPL患者既往生育次数较少。
这是第一项证明希腊RPL女性中TNF-α 238和TNF-α 308基因表达以及不存在TNF-α 376变体的研究。然而，所研究的每种多态性与复发性流产的发生之间均未出现关联。因此，TNF-α -308G>A、-238G>A和-376G>A变体不被视为希腊人群中识别复发性流产风险增加女性的遗传标志物。
