[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 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.


CONCLUSIONS
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.
Guan
Li-xue
LX
Department of Genetics, Weifang People's Hospital, Weifang Medical College, Weifang, Shandong, 261041, PR China. guan373@ public.wfptt.sd.cn
Du
Xin-ying
XY
Wang
Jing-xian
JX
Gao
Li
L
Wang
Rui-li
RL
Li
Hai-bo
HB
Wang
Shou-xun
SX
D000026:Abortion, Habitual / Q000235:genetics*; D000328:Adult; D000483:Alleles; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006801:Humans; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D017395:Plasminogen Activator Inhibitor 1 / Q000235:genetics*; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic / Q000235:genetics*; D012150:Polymorphism, Restriction Fragment Length; D011247:Pregnancy; D055815:Young Adult
D017395:Plasminogen Activator Inhibitor 1; D042965:Methylenetetrahydrofolate Reductase (NADPH2)