PAI-1基因和MTHFR基因多态性与复发性早期自然流产的关系

目的探讨纤溶酶原激活剂抑制物1(plasminogenactivatorinhibitor1,PAI1)基因和亚甲基四氢叶酸还原酶(methylenetetrahydrofolatereductase,MTHFR)基因多态性与复发性早期自然流产(recurrentearlyspontaneousabortion,RESA)的相关性。方法选取127例RESA非妊娠患者和117名健康非妊娠妇女,应用聚合酶链反应限制性片段长度多态性分析技术检测PAI1基因-675位4G/5G多态性和MTHFR基因C677T位点多态性。结果(1)患者组PAI1基因4G/4G基因型频率(45.7%)和4G等位基因频率(66.1%)显著高于对照组(17.1%和46.6%)(P<0.01),与5G/5G基因型比较,4G/4G型患者发生RESA的相对风险率的比数比(oddsratio,OR)为4.8,95%的可信区间(confidenceinterval,CI):2.23～10.35;(2)MTHFR基因T/T基因型和T等位基因频率患者组(43.3%和66.5%)显著高于正常对照组(21.4%和52.6%)(P<0.01),与C/C基因型比较,T/T型患者发生RESA的相对风险率为OR=3.2,95%CI:1.40～7.30;(3)RESA患者若同时兼有4G/4G和T/T基因型时,发生自然流产的相对风险率明显增加,OR=6.20,95%CI:2.62～14.67。结论PAI1基因4G/5G多态性和MTHFR基因C677T位点多态性与不明原因RESA密切相关,易感基因型4G/4G型和T/T型对RESA的发生具有协同作用。

Association of genetic polymorphisms in plasminogen activator inhibitor-1 gene and 5,10-methylenetetrahydrofolate reductase gene with recurrent early spontaneous abortion

Objective To explore the relationship of plasmi no gen activator inhibitor-1 (PAI-1) gene-675 4G/5G and methylenetet rahydrofolate reductase(MTHFR) gene C677T polymorphisms to recurrent early spontaneous abo rtio n(RESA). Methods One hundred and twenty-seven currently non-p regnant women with at least 3 unexplained spontaneous abortions during the firs t trimester of pregnancy (patient group).Normal control group consisted of 117 c urren tly non-pregnant women with at least 1 pregnancy and without a history of prema turity, miscarriage, stillbirth, eclampsia and other pregnancy complications. Th e genotypes of PAI-1 gene and MTHFR gene were assessed by poly merase chain reaction-restrictive fragment length polymorphism. Result s The frequencies of 4G/4G genotype and 4G allele of PAI-1 were higher in patient group (45.7% and 66.1%) than in normal controls (17.1% and 46.6%) (P<0.01). The PAI-1 4G/4G genotype was signi ficantly associated with RESA (OR=4.8,95% CI:2.23-10.35). Besides, MTHFR ge ne T/T genotype and T allele frequencies were increased in RESA patients(43.3% a nd 66.5%) versus normal controls(21.4% and 52.6%)(P<0.01). The patients carr ying T/T genotype had a high risk of early spontaneous abortion(OR=3.2,95% CI:1 .40-7.30).In addition,the presence of the PAI-1 gene 4G/4G genot ype together with the T/T genotype of the MTHFR gene was found to be a risk factor (OR=6.20,95% CI:2.62-14.67) for RESA greater than the 4G/4G genotype or the T/T genotype alone. Conclusion The above findings suggest that genetic polymorphisms of PAI-1 4G/5G and MTHFR C677T were associated with RESA. They may have synergetic impact and present gene dosage ef fect on the susceptibility to the development of early spontaneous abortion.