Angiotensin-converting enzyme insertion/deletion (ACE I/D) and angiotensin II type 1 receptor (AT1R) gene polymorphism and its association with preeclampsia in Chinese women.

OBJECTIVE: To investigate whether polymorphisms of angiotensin converting enzyme gene (ACE) and angiotensin II receptor type 1 gene (AT1R) are associated with etiology of preeclampsia and renal impact in women with preeclampsia. METHODS: DNA was extracted from peripheral blood of 133 patients with preeclampsia and 105 healthy pregnant women. The I/D polymorphism of the ACE gene was assessed by polymerase chain reaction, and the A1166C polymorphism of the AT(1)R gene was additionally assessed by DdeI digestion. The level of proteinuria, fasting serum urea, creatinine and uric acid were investigated according to different genotypes of ACE and AT1R genes. RESULTS: The frequency of genotypes of the ACE gene and the AT1R gene was similar in preeclampsia and normal pregnancy. DD and ID genotype predominated in patients with severe proteinuria, as well as increased serum urea and uric acid. Serum creatinine was also increased, but no significant difference was found among three genotypes. The level of proteinuria, serum uric acid, urea, and creatinine did not vary between different AT1R genotypes. Compared with patients without renal dysfunction, the frequency of DD and ID genotypes of ACE gene was much higher in those with renal dysfunction, but AC and CC genotypes of AT1R gene were not. CONCLUSION: We found no association of the two gene polymorphisms with preeclampsia. However, ACE gene I/D polymorphisms were associated with the severe proteinuria and renal dysfunction seen in preeclampsia. Preeclampsia patients carrying the D allele may be susceptible to renal dysfunction.     

The significance of beta-3 adrenergic receptor polymorphism in excessive body gain and obesity development in pregnant women

The current knowledge allows for the definition of the genetic factors contributing to pathological body mass gain and obesity development. One of the possible candidates is the gene of beta3-adrenergic receptor (ADRB3). Due to the fact that the basic function of this receptor is the induction of thermogenesis process and an increase of energy expenditure, the significance of Trp64Arg polymorphism of ADRB3 gene in disturbances of metabolic processes, which may induce disturbances of adipocytes function and lead to excessive body mass gain, obesity and early beginning of diseases connected with obesity (dyslipidemia, obesity, chronic hypertension, diabetes mellitus type II), has been suggested. The investigations performed in pregnant women concern, in the majority of cases, women with obesity, diabetes mellitus and gestational hypertension. These studies indicate the possible correlation of higher value of body mass index (BMI) with the presence of mutated 64Arg allele. In healthy pregnant women the relationship between Trp64Arg polymorphism of ADRB3 receptor and body gain has been suggested. Additionally, in female carries of the mutated 64Arg allele, a higher placenta mass and birth mass of newborns have been noted. This publication is merely single voice in the discussion because only one cause of excessive body gain and obesity presented here - Trp64Arg polymorphism of ADRB3 receptor. The problem seems to be more complicated and requires an investigation of the influence of other genetic and environmental factors, and the future populate investigations in Trp64Arg polymorphism of ADRB3 receptor.     

Maternal and fetal angiotensin-converting enzyme gene insertion/deletion polymorphism not associated with pregnancy-induced hypertension in Chinese women

Objective.?The study aimed to investigate whether maternal and fetal angiotensin-converting enzyme (ACE) gene insertion/deletion (I/D) polymorphisms and the incompatibility of maternal and fetal ACE genotype are associated with the risk of pregnancy-induced hypertension (PIH) in Chinese Han women.

Methods.?Using a case-control mother-baby dyads study, a total of 226 maternal/offspring pairs were selected at Anyang Maternal and Child Health Hospital from January 2008 to December 2009. Maternal venous and cord bloods were obtained for DNA extraction. A polymerase chain reaction was performed on the genomic DNA samples to obtain the ACE gene I/D polymorphism.

Results.?In the present sample, there is no difference in maternal and fetal ACE genotype or allele frequency between PIH patients and control group (p?>?0.05). Furthermore, no significant association was found between the genotype incompatibility of fetal and maternal ACE gene and the risk of PIH (p?>?0.05).

Conclusion.?We did not find fetus ACE gene I/D polymorphism to be associated with the risk of PIH. Nor is there any evidence that the incompatibility of fetal and maternal ACE genotype is associated with PIH in the studied population.     

ACE基因I/D多态性与子痫前期高血压和肾脏损害关系的研究

目的探讨血管紧张素转换酶（ACE）基因插入／缺失（I／D）多态性与子痫前期患者高血压和肾脏损害程度的相关性。方法选择子痫前期患者82例，正常孕妇45例，利用多聚酶链反应（PCR）分析其外周血白细胞中ACE基因多态性，计数两组孕妇ACE基因型和等位基因分布频率，比较不同基因型子痫前期患者高血压程度和肾功能。结果根据插入／缺失片段的有无，将ACE基因分为DD、ID、II三种基因型，子痫前期患者和正常孕妇ACE基因型和等位基因频率无统计学差异。子痫前期患者中携带D等位基因孕妇的收缩压和舒张压呈升高趋势，血清尿酸含量显著增加，但肌酐、尿素氮水平无统计学差异。结论ACE基因与子痫前期肾脏损害密切相关，携带D等位基因的子痫前期患者肾脏损害严重，血压也有升高趋势，提示D等位基因可能是子痫前期患者病情加重的不利因素。     

Angiotensin converting enzyme gene insertion/deletion polymorphism in patients with polycystic ovary syndrome

Objective.?The aim of this study is to investigate the relevance of polymorphism in angiotensin converting enzyme (ACE) gene insertion/deletion (I/D) polymorphism to the pathophysiology of polycystic ovary syndrome (PCOS).

Subjects and methods.?Thirty patients with PCOS by Rotterdam consensus criteria and 33 control subjects were prospectively investigated. ACE gene amplification of DNA was performed by polymerase chain reaction. Homeostatic model assessment (HOMA-IR) was applied.

Results.?Compared to controls, ACE gene DD genotype and D allele were observed more frequently in PCOS (63% vs. 46% for DD genotype and 75% vs. 67% for D allele) (p?>?0.05). Body mass index, fasting glucose and insulin levels, HOMA-IR index and total testosterone levels were higher in PCOS group (p?<?0.05). The frequencies of D and I alleles were 45 (75%) and 15 (25%) for PCOS group and 44 (67%) and 22 (33%) for control group (p?>?0.05). No significant differences were observed in the genotype and allele distributions between cases and control groups. HOMA-IR index was significantly higher in patients with PCOS with DD genotype than those with II genotype (p?<?0.05).

Conclusion.?The ACE gene polymorphism was not associated with PCOS. However, the presence of D allele was associated with higher rate of insulin resistance in patients with PCOS.     

The protective effect of the ER22/23EK polymorphism against an excessive weight gain during pregnancy

It has been shown that women who gained an excessive weight during pregnancy had an increase in long-term BMI compared with those without an excessive weight gain. Several studies have demonstrated that some polymorphisms of the glucocorticoid receptor (GR) gene may influence body composition and metabolic parameters. In the present study, we wanted to explore whether any association could exist between the BclI, N363S and ER22/23EK polymorphisms of the GR gene and the weight gain during pregnancy. We found that the allelic frequencies of the BclI, N363S and ER22/23EK polymorphisms in 300 women with uncomplicated pregnancies were similar to those measured in healthy Hungarian population. None of the three polymorphisms associated with body weight or BMI at the 1st trimester of pregnancy or before delivery. However, a significantly lower weight gain (p = 0.044) and consequently lower increase of BMI during pregnancy (p = 0.044) was observed in heterozygous carriers of the ER22/23EK polymorphism. These results support a protective role of the ER22/23EK polymorphism against an excessive weight gain and excessive increase of BMI during uncomplicated pregnancy.     

Maternal and neonatal outcomes in women with twin pregnancies with excessive gestational weight gain

Objective: To determine if an excessive rate of gestational weight gain (GWG) in twin pregnancies is associated with adverse obstetric outcomes.

Methods: Retrospective cohort study of twin pregnancies delivered at the University of California, San Diego 2001–2014. Women were included if they had adequate or excessive rates of GWG as determined by Institute of Medicine guidelines. Demographic and outcome variables were collected by chart review.

Results: Four hundred and eighty-nine twin pregnancies met inclusion criteria. Of which, 40.5% had adequate rates of GWG and 41.5% had excessive rates of GWG. The rates of preterm birth and gestational diabetes were similar between the two groups. Gestational hypertension and preeclampsia were more common in women with excessive GWG (37.9% versus 19.7%; p?<?0.01). This finding persisted in multivariate analysis. The mean birth weight percentiles were higher in the excessive GWG group and these women were also less likely to have an infant with a birth weight <10th percentile (21.4% versus 35.9%, p?<?0.01).

Conclusions: Excessive GWG is associated with a higher risk for gestational hypertension and preeclampsia, but no other adverse perinatal outcomes. Infants born to mothers with excessive GWG are less likely to be small for gestational age than those born to women with adequate GWG.     

血管紧张素转化酶基因插入/缺失多态性及胰岛素受体亚单位-1基因Gly972Arg突变对出生体重的影响

目的 探讨血管紧张素转化酶(angiotensin converting enzyme,ACE)基因插入/缺失(insertion/deletion,I/D)多态性及胰岛素受体亚单位-1(insulin receptor substrate-1,IRS-1)基因Gly972Arg突变对出生体重的影响.方法 将入选296例新生儿分为两组,适于胎龄儿组222例,小于胎龄儿组74例,于生后3 d哺乳前检测血糖、胰岛素,计算HOMA-IR值比较两组的胰岛素敏感性;应用PCR-RFLP方法分析IRS-1基因Gly972Arg突变及ACE基因I/D多态性,比较各基因型组间出生体重、出生体重百分位.结果 小于胎龄儿组HOMA-IR值(Ln对数转换后)为0.217±0.367,高于适于胎龄儿组0.001±0.378(P<0.01).IRS-1基因突变组与野生型相比,出生体重较轻,分别为(2270.00±638.97)g及(2655.53±774.78)g,出生体重百分位较低,分别为(13.12±10.76)%及(39.87±30.18)%,差异均有统计学意义(P<0.05).ACE基因DD基因型出生体重百分位为(27.05±24.70)%,低于ID基因型(39.21±29.37)%及Ⅱ基因型(44.69±27.91)%,差异有统计学意义(P<0.05).同时具有ACE基因DD基因型及IRS-1基因突变者出生体重最低(2516.00±230.28)g,低于正常组(2919.87±717.04)g及具有一种基因多态性组(2572.44±724.20)g;其出生体重百分位也最低(18.00±14.89)%,低于正常组(44.97±27.07)%及具有一种基因多态性组(26.95±20.70)%,差异均有统计学意义(P<0.05).结论 IRS-1基因Gly972Arg突变及ACE基因I/D多态性可能对胎儿宫内发育和出生体重具有影响.     

Angiotensin-converting enzyme insertion/deletion (I/D) polymorphisms and recurrent pregnancy loss: a meta-analysis

Background

Recurrent pregnancy loss (RPL) had said to be related to the angiotensin converting enzyme insertion/deletion polymorphisms (ACE I/D) gene polymorphisms. But the conclusions were controversial. This meta-analysis was conducted to investigate the real association in ACE I/D polymorphisms and RPL firstly.

Methods

Combine Pubmed Embase and HuGENet database in data analysis for this meta-analysis from October 2000 to November 2011. The metagen system was used to select the models and effects. Odds ratio (OR) with 95% confidence interval (CI) was used to assess the strength of this association.

Results

9 studies from six countries with 1264 RPL and 845 controls were included according to our criterion. Following the metagen system, we used the dominant model with random effects. The summary OR =1.61 (95% CI: 1.10-2.36, I² = 59.0%), which suggested the ACE D allele might increase the RPL risk in Asia (OR=1.97, 95% CI: 1.31-2.98, I² = 44.4%), among Asians (OR=1.69, 95% CI: 1.06-2.36, I² =32.7%). In additional, after conducting sensitivity analysis, the results had no differences except for Caucasian subgroup reached to the significance (OR=2.059, 95% CI: 1.455-2.914), so we couldn’t ignore the relationship between the polymorphisms of ACE D/I gene and Caucasians yet. There seemed no publication bias in our eligible studies with Begg’s test (P = 0.867).

Conclusions

Results in this meta-analysis presented the positive function of the ACE I/D polymorphism in increasing the RPL risk. Furfure prospective studies were needed to confirm the precise relationship between the ACE I/D and RPL.     

Associations of polymorphisms of the angiotensinogen M235 polymorphism and angiotensin-converting-enzyme intron 16 insertion/deletion polymorphism with preeclampsia in Korean women

OBJECTIVE: The contribution of genetic factors to preeclampsia has been well documented. However, there has not been any study done on the association between preeclampsia and the angiotensinogen (AGT) M235T polymorphism and angiotensin-converting-enzyme (ACE) intron 16 insertion/deletion (I/D) polymorphism among Korean preeclampsia women. We performed a hospital-based case-control study on Korean women to investigate the association between preeclampsia and the angiotensinogen M235T polymorphism and also to determine the association between preeclampsia and the angiotensin-converting-enzyme intron 16 polymorphism. METHODS: DNA was extracted from whole blood of 104 preeclampsia patients and 114 healthy pregnant women. All samples were genotyped for all the polymorphisms using amplification after PCR of known allelic variants. Results were analyzed with the chi-square test, Student's t-test, and logistic regression. RESULTS: 18 of 50 women with preeclampsia (36.0%) in nulliparous women and 15 of 37 women with preeclampsia (40.5%) in parous women were homozygous for methionine (M235) to threonine (T235) substitution at residue 235 of AGT gene, versus 12 of 38 women in nulliparous control women and 18 of 50 women in parous control women. There was no association between the AGT M235T polymorphism and preeclampsia according to age. Fourteen of 55 women with preeclampsia (25.5%) in nulliparous women and 11 of 39 women with preeclampsia (28.2%) in parous women were homozygous for the D allele of the ACE intron 16, versus 9 of 52 women in nulliparous control women and 16 of 53 women in parous control women. No association was demonstrated between D allele of ACE intron 16 and preeclampsia according to age. There were significant differences in birth weight and delivery weeks between controls and preeclampsia patients (P < 0.001). There were no significant differences in age and nulliparity between controls and preeclampsia patients. CONCLUSION: The result indicates that the AGT M235T polymorphism and the ACE intron 16 polymorphism play no significant role in preeclampsia observed in Korean women.     

血管紧张素转化酶基因插入或缺失多态性与新生儿危重症关系的研究

目的 检测血管紧张素转化酶（angiotensin converting enzyme，ACE）基因型，探讨ACE基因插入或缺失多态性与新生儿危重症的关系。方法 451例新生儿分为：正常对照组116例，按新生儿危重病例评分标准将入NICU者于入院第1天分为非危重病组237例和危重病组98例。提取DNA进行基因分型。结果 危重病组比正常对照组、非危重病组DD基因型频率高、Ⅱ基因型频率低。DD基因型危重病评分低于ID和Ⅱ（P〈0．01），ID和Ⅱ基因型间无差异（P〉0．05）。DD基因型新生儿呼吸窘迫综合征发病率11．5％、新生儿湿肺发病率13．5％，需要呼吸机治疗者18．8％，高于ID＋Ⅱ的3．9％、6．2％和8．7％，差异均有统计学意义（P均＜0．05）。DD基因型发生代谢性酸中毒17．7％、低钠血症19．8％、低血糖症35．4％，高于ID＋Ⅱ的8．4％、11．5％和23．4％，差异均有统计学意义（P均〈0．05）。247例早产儿中，发生动脉导管未闭DD基因型21．6％，高于ID＋Ⅱ的9．7％（P〈0．05）。结论 ACE基因插入或缺失多态性与新生儿危重症有相关性。DD基因型患儿病情相对重，心肺功能适应性相对差。     

原发性肾病综合征患儿血管紧张素原和血管紧张素转换酶基因多态性的检测与临床分析

目的探讨北方汉族原发肾病综合征(PNS)儿童血管紧张素原(AGT)基因M235T单核苷酸与血管紧张素转换酶(ACE)基因多态性的关系。 方法研究对象为2001—2005年首都医科大学附属儿童医院住院的148例北方汉族PNS患儿及50例正常儿童，采用聚合酶链反应-限制性片段长度多 态性方法检测AGT(M235T)、ACE(I/D)的多态性。 结果PNS组携带ACE基因DD型、D等位基因、AGT基因MT型及同时携带D、T等位基因的频率高于正常对照组(P分别为0.004、0.032、0.036、0.004) 。复发组D等位基因频率高于非复发组(P=0.000)。PNS患儿中高胆固醇+高三酰甘油(甘油三脂)血症组DD基因频率高于正常组(P=0.006)。激素耐 药组DD基因频率(34.21%)高于激素敏感组(20.91%)。ACE基因的插入序列长度为289bp，存在2处单核苷酸多态性，分别为第103、151位各插入1 个G。 结论携带ACE基因D等位基因、AGT基因MT型、同时携带D(DD/ID)、T(MT/TT)等位基因的北方汉族儿童为PNS的易感人群。携带ACE(DD)基因PNS患 儿易复发、可能易合并高胆固醇及高三酰甘油血症，可能会有激素耐药倾向。ACE基因插入序列长度及核苷酸序列与国外报道不同。     

Patterns of gestational weight gain in healthy,low-risk pregnant women without co-morbidities

Background

little is known of the impact of gestational weight gain (GWG) in relation to Body Mass Index (BMI) classification on perinatal outcomes in healthy pregnant women without co-morbidities. As a first step, the prevalence of obesity and the distribution of GWG in relation to the Institute of Medicine (IOM) 2009 guidelines for GWG were examined.

Methods

data from a prospective cohort study of – a priori – low risk, pregnant women from five midwife-led practices (n=1449) were analysed. Weight was measured at 12, 24 and 36 weeks.

Findings

at 12 weeks, 1.4% of the women were underweight, 53.8% had a normal weight, 29.6% were overweight, and 15.1% were obese according to the WHO classification of BMI. In our study population, 60% of the women did not meet the IOM recommendations: 33.4% had insufficient GWG and 26.7% gained too much weight. Although BMI was negatively correlated to total GWG (p<.001), overweight and obese women class I had a significant higher risk of exceeding the IOM guidelines. Normal weight women had a significantly higher risk of gaining less weight than recommended. Obese women classes II and III were at risk in both over- and undergaining.

Conclusions

our data showed that the majority of women were unable to stay within recommended GWG ranges without additional interventions. The effects on pregnancy and health outcomes of falling out the IOM guidelines remain unclear for – a priori – low risk women. Since interventions to control GWG would have considerable impact on women and caregivers, harms and benefits should be well-considered before implementation.     

Physical activity level and weight gain in a cohort of pregnant Norwegian women

BACKGROUND: It is generally recommended that healthy, pregnant women should engage in moderate exercise on most days of the week. However, there is scant knowledge about the overall physical activity and exercise levels among pregnant women. PURPOSE: To assess the total physical activity level of pregnant women, and to investigate the association between weight gain, physical activity and exercise during pregnancy. METHODS: Pregnant women (n=467) answered a questionnaire on total physical activity level in gestation week 36. RESULTS: Some 55% of the participants reported working in a sitting position. Most women drove (52.9%) or used public transport (31.7%) to work. A total of 39% reported sedentary activities of>or=4 h (watching television and reading) daily; 19% were defined as non-exercisers before pregnancy, 30% in the first trimester, 36% in the second trimester and 53% in the third trimester. Fifty women (10.6%) continued to exercise>or=4 times/week in the third trimester. Mean weight gain was 13.8 kg (SD: 5.2). Of the normal pregestational weight women (pre-BMI: <26) and overweight women (pre-BMI: >or=26), 32 and 51% had exceeded weight gain above accepted recommendations, respectively. Women who exercised regularly had significantly lower weight gain than inactive women in the third trimester only. CONCLUSION: Pregnant women have a low total physical activity level, and a high percentage of women exceed the recommended weight gain during pregnancy.     

钙蛋白酶10基因多态性与妊娠期糖代谢异常的关系

目的 探讨孕妇钙蛋白酶10基因单核苷酸多态性(SNP)43、SNP-19和SNP-63与妊娠期糖代谢异常发生风险之间的关系.方法 选择2005年1月至2006年12月在北京大学第一医院分娩的156例妊娠期糖代谢异常患者(妊娠期糖代谢异常组)和114例孕周匹配的健康孕妇(对照组),应用引物引入限制性内切酶分析-聚合酶链反应方法检测两组孕妇钙蛋白酶10基因SNP-43、SNP-19和SNP-63的基因型.结果 (1)在妊娠期糖代谢异常组中,钙蛋白酶10基因SNP-19的基因型2R/2R频率(26.9%,42/156)和等位基因2R频率(48.9%,152/312)明显高于对照组[分别为12.3%(14/114)和36.8%(84/228)],分别比较,差异均有统计学意义(P=0.012,P=0.006).(2)根据有无糖尿病家族史分层分析发现,在家族史阳性的妊娠期糖代谢异常组中SNP-19基因型2R/2R+2R/3R分布占83%(47/57),明显高于对照组的52%(11/21,P=0.009),SNP-43基因型T/T+T/C分布占47%(27/57),明显高于对照组的14%(3/21,P=0.026).(3)对SNP-43、SNP-19和SNP-63位点进行单体型分析,发现在妊娠期糖代谢异常组中单体型121所占的比例明显高于对照组(P=0.036),而单体型221所占的比例明显低于对照组(P=0.042).结论 (1)钙蛋白酶10基因SNP-19多态性与妊娠期糖代谢异常有关,2R等位基因可能是妊娠期糖代谢异常发生的高危因素.SNP-19的基因型2R2R+2R/3R和SNP-63的基因型T/T+T/C可增加糖尿病家族史阳性个体妊娠期糖代谢异常的发生风险,而不影响家族史阴性个体的发病风险.(2)钙蛋白酶10基因SNP-43、SNP-19和SNP-63组成的单体型121可能是妊娠期糖代谢异常发生的高危因素,单体型221可能是其保护因素.