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

Zhonghua Yi Xue Yi Chuan Xue Za Zhi

Department of Genetics, Weifang People's Hospital, Weifang Medical College, Weifang, Shandong, 261041, PR China. guan373@ public.wfptt.sd.cn

Published: June 2005

Objective: To explore the relationship of plasminogen activator inhibitor-1 (PAI-1) gene-675 4G/5G and methylenetetrahydrofolate reductase(MTHFR) gene C677T polymorphisms to recurrent early spontaneous abortion(RESA).

Methods: One hundred and twenty-seven currently non-pregnant women with at least 3 unexplained spontaneous abortions during the first trimester of pregnancy (patient group). Normal control group consisted of 117 currently non-pregnant women with at least 1 pregnancy and without a history of prematurity, miscarriage, stillbirth, eclampsia and other pregnancy complications. The genotypes of PAI-1 gene and MTHFR gene were assessed by polymerase chain reaction-restrictive fragment length polymorphism.

Results: 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 significantly associated with RESA (OR = 4.8, 95% CI: 2.23 - 10.35). Besides, MTHFR gene T/T genotype and T allele frequencies were increased in RESA patients (43.3% and 66.5%) versus normal controls (21.4% and 52.6%) (P < 0.01). The patients carrying T/T genotype had a high risk of early spontaneous abortion (OR = 3.2, 95% CI: 1.40 - 7.30). In additionìthe presence of the PAI-1 gene 4G/4G genotype 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 effect on the susceptibility to the development of early spontaneous abortion.

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