Association of leptin level and leptin receptor gene polymorphisms with susceptibility to severe pre-eclampsia / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To evaluate the association of serum leptin concentrations and polymorphisms of G1019A and A223G of leptin receptor gene (LEPR) with severe pre-eclampsia. MEHTODS: A case-control study was carried out in 207 patients with severe pre-eclampsia (SPE group) and 252 healthy pregnant women (control group) during the third trimester of pregnancy. The serum leptin was determined by enzyme-linked immunosorbent assay. The polymorphisms of LEPR gene G1019A and A223G were detected by polymerase chain reaction restriction-fragment length polymorphism (PCR-RFLP) analysis. Miettinen's test was used to estimate the odds ratios (OR) and 95% confidence intervals (CI).</p><p><b>RESULTS</b>(1) In severe pre-eclampsia group, serum leptin levels and rate of premature infant birth were significantly higher than that in normal pregnant women, and birth weight was lower than that in controls (P<0.01). (2) The frequencies of GA genotype and G allele for LEPR gene G1019A in SPE group (33.8% and 20.3%) were markedly higher than that in controls (19.8% and 15.1%) (P<0.01), and the carriers of GA genotype and G allele were more frequent in SPE group than in control group, resulting in an OR 2.04 (95%CI: 0.77-5.42) and 1.43 (95%CI: 1.02-2.01) to develop severe pre-eclampsia, compared with carriers of AA genotype and A allele. (3) AG genotype and A allele frequencies of LEPR gene A223G in SPE group (19.3% and 12.6%) were significantly lower than that in controls (34.5% and 19.2%) (P<0.01), resulting in an OR of 0.46 (95%CI: 0.30-0.71) and 0.60 (95%CI: 0.42-0.87) to develop severe pre-eclampsia, compared with subjects with GG genotype and G allele. (4) The "1019AA+223AG" genotype frequency was significantly lower in SPE group (6.8%) than in controls (24.6%) (P<0.01), resulting in an OR of 0.22 (95%CI: 0.12-0.39) to develop severe pr-eclampsia, while the "1019AA+223AG" was significantly higher in SPE group (22.2%) than in controls (11.9%) (P<0.05), resulting in an OR of 2.10 (95%CI: 0.78-3.45) to develop severe pre-eclampsia. (5) No significant differences were found in SBP, DBP, BMI and serum leptin levels in subjects with different genotypes in the two groups (P>0.05).</p><p><b>CONCLUSION</b>Elevated serum leptin level and LEPR gene G1019A and A223G polymorphisms might play a role in severe pre-eclampsia, while the level of serum leptin was not associated with genotypes of LEPR gene G1019A and A223G polymorphisms. The genotypes GA and "1019AA+223AG"of G1019A may be genetic susceptibility factors to severe pre-eclampsia.</p>

Association of genetic polymorphisms in plasminogen activator inhibitor-1 gene and 5,10-methylenetetrahydrofolate reductase gene with recurrent early spontaneous abortion / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>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).</p><p><b>METHODS</b>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.</p><p><b>RESULTS</b>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.</p><p><b>CONCLUSION</b>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.</p>

Relationship between the 4G/5G polymorphism of the plasminogen activator inhibitor-1 gene and the pathogenesis of pregnancy-induced hypertension syndrome / 中华医学遗传学杂志

<p><b>OBJECTIVE</b>To investigate the relationship between a single nucleotide insertion/deletion(4G/5G) polymorphism located in the promoter region of the plasminogen activator inhibitor-1(PAI-1) gene and the pathogenesis of pregnancy-induced hypertension syndrome(PIHs).</p><p><b>METHODS</b>The 4G/5G polymorphism of PAI-1 gene in 171 PIHs patients (PIHs group) and that in 193 normal pregnant women (control group) were detected by a combination of polymerase chain reaction-restriction fragment length polymorphism.</p><p><b>RESULTS</b>(1)The genotype frequencies of PAI-1 gene in PIHs group were 47.4% for 4G/4G, 41.5% for 4G/5G, and 11.1% for 5G/5G. The 4G/4G genotype and 4G allele frequencies of PAI-1 gene(47.4% and 0.681) for PIHs patients were higher than those (21.2% and 0.495) for normal controls respectively (P<0.001). (2)Both the 4G/4G genotype and the 4G allele of PAI-1 gene occurred more frequently in the severe PIHs group(61.3% and 0.758) than those (35.8% and 0.623) in the mild PIHs group respectively (P<0.001). However, there were no significant differences between those in mild group (35.8% and 0.623) and moderate group(42.8% and 0.625) respectively. (3) The 4G/4G genotype was significantly associated with PIHs (OR=3.34, 95%CI: 2.14-5.22).</p><p><b>CONCLUSION</b>These findings suggested that PAI-1 gene polymorphism may be a susceptible factor to the pathogenesis of PIHs and the 4G/4G genotype may be one of the major risk factors for PIHs in pregnant women.</p>