OBJECTIVE: To investigate the association of the polymorphism of angiotensin-converting enzyme (ACE) gene and pregnancy-induced hypertension (PIH) in Chinese Women. METHODS: We systematically searched CNKI, Wanfang database, VIP and PubMed from database construction to March 2012 to collect case-control studies. Stata 11.0 was used for meta analysis after evaluating the quality of studies and collecting the data. The association was assessed by odds ratio (OR) with 95% confidence intervals (CIs). Publication bias was analyzed by Begg's funnel plot and Egger's regression test. RESULTS: We identified 11 case-control studies on association between ACE gene polymorphism and PIH, which included 806 PIH patients and 900 controls. Overall, significant association was found between ACE gene polymorphism and PIH risk [for D vs I: OR=2.73, 95% CI (1.64, 4.24), P<0.001; for DD+DI vs II: OR=3.11, 95% CI (1.98, 4.90), P<0.001; for DD vs II: OR=5.00, 95% CI (2.30,10.88), P<0.001; for DI vs II: OR=1.97, 95% CI(1.53, 2.53), P<0.001]. CONCLUSION Chinese women with D allele gene deletion have a higher risk of suffering pregnancy induced hypertension syndrome.
Adult ; Alleles ; Female ; Genetic Predisposition to Disease ; Humans ; Hypertension, Pregnancy-Induced ; genetics ; INDEL Mutation ; Peptidyl-Dipeptidase A ; genetics ; Polymorphism, Genetic ; Pregnancy ; Randomized Controlled Trials as Topic ; Risk Factors

To study whether the development of hypertensive disorder complicating pregnancy is associated with -308G-->A, -850C-->T mutation at promoter of TNF-alpha gene, the -308G-->A, -850C-->T polymorphism was examined in patients and healthy pregnant women by PCR-RFLP technique. The frequencies of genotype and allele were compared between the two groups. The results showed that with -308G-->A polymorphism distribution, the allele frequency of TNF2 and the frequency of the genotype TNF2/1 in the patient group was significantly higher in the patient group than in control group (P<0.05). A significant difference in genotype distribution of -850C-->T polymorphism was observed between the two groups. The allele frequencies of T in patient group was higher in the control group as compared with the patient group. The frequencies of CT and TT genotypes were lower in the patient group. It is concluded that the TNF2 allele of -308 is associated with the occurrence of hypertensive disorder complicating pregnancy, while T allele of -850 may be the protective factor against the development of the disease. TNF2/1 CC may be susceptibility genotype of hypertensive disorder complicating pregnancy.
Case-Control Studies ; Gene Frequency ; Genotype ; Hypertension, Pregnancy-Induced/*genetics ; Mutation/*genetics ; Polymorphism, Genetic/*genetics ; Promoter Regions, Genetic ; Tumor Necrosis Factor-alpha/*genetics ; Young Adult

Animals ; Female ; Hypertension, Pregnancy-Induced ; metabolism ; pathology ; Kidney ; metabolism ; pathology ; Pregnancy ; Protein Kinase C-alpha ; genetics ; metabolism ; Rats ; Rats, Wistar ; Transcription, Genetic

BACKGROUNDThe mechanisms responsible for the pathogeneses of gestational hypertension and preeclampsia are unclear. Tumor necrosis factor-alpha (TNF-alpha) is a pro-inflammatory Th(1)-type cytokine. TNFA gene is located in the human leukocyte antigen (HLA) class III region of the major histocompatibility complex (MHC) on chromosome 6. The high TNF-alpha mRNA expression may be associated with the TNF2 (A) allele, which is the polymorphism of TNF-alpha at position -308 in promoter region. This study assessed whether the TNF2 (A) allele at position -308 plays a role in the alteration of blood pressure (BP) and urinary protein excretion during pregnancy.

METHODSThe original prospective cohort study comprised 1623 pregnant women from January 2000 to October 2001. The G/A polymorphism was done by restriction fragment length polymorphism (RFLP) analysis with Nco I enzyme.

RESULTSThe distributions of the G/A polymorphism of TNF-alpha in the promoter region at position -308 were wild-type 72.4% and variant 27.6%, respectively. The frequency of TNF2 (A) allele was approximately 0.15 for Caucasian pregnant women in the study. It was not significantly different in the distributions of genotypes and G/A allele frequencies among the three groups of pregnant women with gestational hypertension, preexisting hypertension and normal blood pressure (P > 0.05). The maternal blood pressure in the third trimester was significantly higher in the group of women possessing the TNF2 (A) allele compared to homozygous for the TNF1 (G) allele (systolic BP, P < 0.01 and diastolic BP, P < 0.05). The elevated blood pressure in the TNF2 (A) group was accompanied by higher urinary protein excretion in the third trimester (P < 0.05). The blood pressure and urinary protein excretion did not change apparently between the two groups in the first and second trimesters (P > 0.05).

CONCLUSIONSMaternal TNF2 (A) allele of TNF-alpha promoter region at position -308 could play a role in the alteration of blood pressures and/or enhancement of urinary protein excretion during pregnancy, and might play an important role in the development of both gestational hypertension and preeclampsia.

Adolescent ; Adult ; Cohort Studies ; Female ; Genetic Variation ; Humans ; Hypertension, Pregnancy-Induced ; genetics ; Middle Aged ; Polymorphism, Genetic ; Pregnancy ; Promoter Regions, Genetic ; Prospective Studies ; Proteinuria ; genetics ; Tumor Necrosis Factor-alpha ; genetics

This study aims to investigate the effect and mechanism of arctigenin(ARC) in the treatment of vascular endothelial injury in rats with pregnancy-induced hypertension(PIH). Fifty SD rats pregnant for 12 days were randomly assigned into a control group, a model group, an ARC group, a rapamycin(RAP, autophagy inducer) group, and an ARC+3-methyladenine(3-MA, autophagy inhibitor) group, with 10 rats in each group. The rats in the other groups except the control group were intraperitoneally injected with nitrosyl-L-arginine methyl ester(50 mg·kg~(-1)·d~(-1)) to establish the PIH model on the 13th day of pregnancy. On the 15th day of pregnancy, the rats in ARC, RAP, and ARC+3-MA groups were intraperitoneally injected with ARC(50 mg·kg~(-1)·d~(-1)), RAP(1 mg·kg~(-1)·d~(-1)), and 3-MA(15 mg·kg~(-1)·d~(-1))+ARC(50 mg·kg~(-1)·d~(-1)), respectively. The pregnant rats in the control group and the model group were intraperitoneally injected with the same amount of normal saline. The blood pressure and 24 h urine protein(24 h-UP) of pregnant rats in each group were measured before and after intervention. Cesarean section was performed to terminate pregnancy on day 21, and the body weight and body length of fetal rats were compared among groups. Hematoxylin-eosin(HE) staining was employed to observe the pathological changes of placenta. The expression of endothelin-1(ET-1) and endothelial nitric oxide synthase(eNOS) in placenta was detected by immunohistochemistry. The serum levels of ET-1 and nitric oxide(NO) were determined with corresponding kits. The expression of microtubule-associated protein 1 light chain 3(LC3), Beclin-1, NOD-like receptor protein 3(NLRP3), apoptosis-associated speck-like protein with CARD domain(ASC), caspase-1, interleukin(IL)-1β, and IL-18 was determined by immunofluorescence and Western blot. The level of reactive oxygen species(ROS) in placenta was measured by fluorescence staining. The results showed that on day 12 of pregnancy, the blood pressure and 24 h-UP had no significant differences among groups. On days 15, 19, and 21, the blood pressure and 24 h-UP in the model group were higher than those in the control group(P<0.05). On days 19 and 21, the blood pressure and 24 h-UP in ARC group and RAP group were lower than those in the model group(P<0.05), and they were higher in the ARC+3-MA group than in the ARC group(P<0.05). On day 21, the model group had lower body weight and body length of fetal rats(P<0.05), higher serum level of ET-1, and lower serum level of NO(P<0.05) than the control group. Moreover, the placental tissue showed typical pathological damage, down-regulated expression of LC3-Ⅱ/LC3-Ⅰ, Beclin-1 and eNOS(P<0.05), up-regulated expression of ET-1, NLRP3, ASC, caspase-1, IL-1β, and IL-18(P<0.05), and elevated ROS level. Compared with the model group, ARC and RAP groups showed increased body weight and body length of fetal rats(P<0.05), lowered serum level of ET-1, elevated serum level of NO(P<0.05), reduced pathological damage of placental tissue, up-regulated expression of LC3-Ⅱ/LC3-Ⅰ, Beclin-1, and eNOS(P<0.05), down-regulated expression of ET-1, NLRP3, ASC, caspase-1, IL-1β, and IL-18(P<0.05), and lowered ROS level. Compared with ARC group, 3-MA reversed the effects of ARC on the above indicators. In conclusion, ARC can inhibit the activation of NLRP3 inflammasome and mitigate vascular endothelial damage in PIH rats by inducing autophagy of vascular endothelial cells.
Female ; Pregnancy ; Animals ; Rats ; Humans ; Rats, Sprague-Dawley ; Hypertension, Pregnancy-Induced/drug therapy* ; Endothelial Cells ; Inflammasomes ; Interleukin-18 ; NLR Family, Pyrin Domain-Containing 3 Protein/genetics* ; Beclin-1 ; Cesarean Section ; Reactive Oxygen Species ; Placenta ; Caspase 1 ; Autophagy