目的 探讨血栓前状态易感基因变异与复发性流产的相关性。方法 选择2021-12至2023-12在解放军总医院第九医学中心就诊的复发性流产患者103例,并选择同期就诊的无自然流产史患者91例作为对照。分别对两组人群的血栓前状态易感基因变异进行检测,包括FVL基因1691 位点、FⅡ基因20210位点、PAI-1基因675位点、MTHFR基因677位点和1298位点。结果 两组FVL基因1691位点、FⅡ基因20210位点均未见杂合变异与纯合变异;两组间PAI-1基因675位点变异(χ2=0.429,P=0.452)、MTHFR基因677位点(χ2=1.346,P=0.510)和1298位点(χ2=2.866,P=0.245)基因变异频率无统计学差异。单因素回归分析显示,PAI-1基因675位点(OR=1.245,95% CI:0.624～2.482,P=0.533),MTHFR基因677位点(OR=1.071,95% CI:0.571～2.009,P=0.830)和1298位点(OR=1.6324,95% CI:0.883～3.017,P=0.117)的基因变异与复发性流产无关。结论 FVL基因、FⅡ基因、PAI-1基因及MTHFR基因变异与复发性流产无相关性,不建议此类患者常规进行遗传性血栓前状态检测。
Abstract
Objective To explore the association between prethrombotic state susceptibility gene variation and recurrent abortion. Methods A total of 103 patients with recurrent abortion from the Ninth Medical Center of PLA General Hospital from December 2021 to December 2023, and 91 patients with no history of spontaneous abortion were selected as controls. Prethrombotic susceptibility gene variants were detected in the two groups, including FVL gene 1691 locus, FⅡ gene 20210 locus, PAI-1 gene 675 locus, MTHFR gene 677 locus and 1298 locus. Results Neither heterozygous nor homozygous variation were detected at locus 1691 of the FVL gene or locus 20210 of FⅡ gene in the two groups. Additionally, no significant differences in mutation frequencies were found between the two groups at locus 675 of the PAI-1 gene (χ2=0.429, P=0.452), locus 677 of the MTHFR gene (χ2=1.346, P=0.510), and locus 1298 of the MTHFR gene (χ2=2.866, P=0.245). Univariate regression analysis indicated that no association between the occurrence of recurrent spontaneous abortion and the frequencies of mutations in the PAI-1 gene at locus 675 (OR=1.245,95% CI:0.624～2.482,P=0.533), the MTHFR gene at locus 677 (OR=1.071,95% CI:0.571～2.009,P=0.830), and locus 1298 (OR=1.6324,95% CI:0.883～3.017,P=0.117). Conclusions Variations of FVL gene, FⅡgene, PAI-1 gene and MTHFR gene are not associated with recurrent abortion, and should not be screened for patients of recurrent abortion.
关键词
复发性流产 /
血栓前状态 /
FVL基因 /
PAI-1基因 /
MTHFR基因
Key words
recurrent abortion /
prethrombotic state /
FVL gene /
PAI-1 gene /
MTHFR gene
{{custom_sec.title}}
{{custom_sec.title}}
{{custom_sec.content}}
参考文献
[1] Green D M,O’Donoghue K.A review of reproductive outcomes of women with two consecutive miscarriages and no living child[J]. J Obstet Gynaecol, 2019, 39(6): 816-821.
[2] 中华医学会妇产科学分会产科学组,复发性流产诊治专家共识编写组.复发性流产诊治专家共识(2022)[J].中华妇产科杂志,2022, 57(9):653-667.
[3] 自然流产诊治中国专家共识编写组.自然流产诊治中国专家共识(2020年版)[J].中国实用妇科与产科杂志, 2020,36 (11):1082-1090.
[4] Shehata H,Ali A,Silva-Edge M,et al.Thrombophilia screening in women with recurrent first trimester miscarriage: is it time to stop testing? A cohort study and systematic review of the literature[J]. BMJ Open, 2022, 12(7): e059519.
[5] Quenby S, Gallos I D, Dhillon-Smith R K,et al.Miscarriage matters: the epidemiological, physical, psychological, and economic costs of early pregnancy loss[J].Lancet,2021,397(10285):1658-1667.
[6] 张丽梅,杨燕宁,张瑞晓,等.自然流产两次与三次及以上的早期复发性流产患者病因构成的比较[J].中华妇产科杂志,2018, 53(12): 855-859.
[7] 国家妇幼健康研究会生殖免疫学专业委员会专家共识编写组.复发性流产合并血栓前状态诊治中国专家共识[J].中华生殖与避孕杂志,2021, 41(10): 861-875.
[8] 王曌华,张建平.血栓前状态与复发性流产及抗凝治疗[J].中国实用妇科与产科杂志,2013,29(2): 102-106.
[9] Liu X, Chen Y, Ye C, et al. Hereditary thrombophilia and recurrent pregnancy loss: a systematic review and meta-analysis[J].Hum Reprod, 2021,36(5):1213-1229.
[10] Bigdeli R,Younesi M R, Panahnejad E,et al.Association between thrombophilia gene polymorphisms and recurrent pregnancy loss risk in the Iranian population[J]. Syst Biol Reprod Med,2018,64(4):274-282.
[11] Wen Y, He H, Zhao K. Thrombophilic gene polymorphisms and recurrent pregnancy loss: a systematic review and meta-analysis[J]. J Assist Reprod Genet,2023,40(7):1533-1558.
[12] Lissalde L G,Fabbro P P,Cochery N E,et al.Factor Ⅴ Leiden and prothrombin G20210A polymorphisms as risk factors for miscarriage during a first intended pregnancy: the matched case-control 'NOHA first' study[J].J Thromb Haemost,2005, 3(10):2178-2184.
[13] Ahangari N,Doosti M,Mousavifar N,et al.Hereditary thrombophilia genetic variants in recurrent pregnancy loss[J]. Arch Gynecol Obstet,2019,300(3):777-782.
[14] Parand A,Zolghadri J,Nezam M,et al.Inherited thrombophilia and recurrent pregnancy loss[J].Iran Red Crescent Med J,2013,15(12):e13708.
[15] Li X, Liu Y, Zhang R,et al.Meta-analysis of the association between plasminogen activator inhibitor-1 4G/5G polymorphism and recurrent pregnancy loss[J].Med Sci Monit,2015,21:1051-1056.
[16] Javan M R,Bahareh M B,Hossein A,et al. The role of thrombophilia factors polymorphism and cytogenetic analysis in recurrent pregnancy loss (RPL) in Northeastern Iran[J].JOGC,2023,8(4): 341-348.
[17] Ren A,Wang J.Methylenetetrahydrofolate reductase C677T polymorphism and the risk of unexplained recurrent pregnancy loss: a meta-analysis[J]. Fertil Steril, 2006, 86(6): 1716-1722.
[18] Bowman Z S,Wünsche V,Porter T F,et al.Prevalence of antiphospholipid antibodies and risk of subsequent adverse obstetric outcomes in women with prior pregnancy loss[J]. J Reprod Immunol, 2015,107:59-63.
[19] Rai R S,Regan L,Clifford K,et al.Antiphospholipid antibodies and beta 2-glycoprotein-I in 500 women with recurrent miscarriage: results of a comprehensive screening approach[J].Hum Reprod,1995,10:2001-2005.
PDF(1270 KB)
