Association of methylenetetrahydrofolate reductase C677T polymorphism with the pre-eclampsia risk in Hakka pregnant women in Southern China

Abstract

The aim of this study is to clarify the possible association between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and pre-eclampsia in Hakka pregnant women in southern China. Pre-eclampsia and normal pregnant women were consecutively collected and MTHFR C677T genotypes were determined by the DNA sequencing method. One hundred and thirteen pre-eclampsia patients were CC homozygote (113 of 191, 59.2%), 68 of 191 (35.6%) were CT heterozygote, and 10 of 191 (5.2%) were TT homozygote, with the frequency of the T allele equal to 0.77. This is in comparison with the normal control group where 106 of 202 (52.5%) were CC homozygote, 83 of 202 (41.1%) were CT heterozygote, and 13 of 202 (6.4%) were TT homozygote, with the frequency of the T allele equal to 0.27. No statistically significant differences were observed in genotype or allele frequencies between the pre-eclampsia and normal control for the C677T polymorphism of MTHFR gene (p?>?.05). The findings of this study suggest that polymorphisms of MTHFR C677T genes were not associated with pre-eclampsia in Hakka pregnant women from southern China, but additional studies are necessary to explore the mechanisms involving it.     

Pre-eclampsia causes adverse maternal outcomes across the gestational spectrum

ObjectiveTo determine if women with early onset pre-eclampsia (EOP) have worse maternal outcomes than those who present later. Specifically, we aimed to determine whether term preeclamptic women and their infants have better outcomes than either their late pre-term or early onset counterparts.Study designBetween 1991 and 2011, 4657 pregnancies complicated by hypertension were recorded in our database; 2148 (45%) had pre-eclampsia (PE). Six hundred ninety six cases (32%) that had accurate data for the gestation at which PE developed were analysed. Pre-eclampsia was defined as per the International Society for the Study of Hypertension in Pregnancy guidelines. Maternal outcomes included (1) episodes of severe hypertension, (2) proteinuria, (3) acute kidney injury, (4) abnormal liver function, (5) thrombocytopenia and (6) neurological complications. Perinatal outcomes were also analysed.ResultsEighty seven (13%) of 696 cases had EOP; 226 (32%) had late pre-term PE and 383 (55%) term PE. Maternal age was similar amongst the three groups. Women with late pre-term and term PE had similar rates of maternal and foetal outcomes. Compared with term PE, women with EOP had similar rates of adverse maternal outcomes, however their babies had significantly increased rates of morbidity and mortality.ConclusionPre-eclampsia causes significant maternal organ involvement regardless of gestation at onset. Outcomes for babies of women with EOP are significantly worse than for those who present later. Overall, women presenting with PE after 34 weeks have generally good maternal and foetal outcomes in a unit equipped to manage such cases.     

Hepatitis B – chronic carrier status and pregnancy outcomes: An obstetric perspective

Antenatal screening for hepatitis B surface antigen (HBsAg) only identifies women with hepatitis B virus (HBV) infection for neonatal immunoprophylaxis. It does not reflect the phase of chronic infection, viral genotype and activity, hepatic inflammation, or other co-existing liver disorders. Coinfection with other viruses and micro-organisms may also be present. These factors in various combinations can impact pregnancy outcomes, and they are probably responsible for the conflicting literature on this issue. Pregnancy complications may interact with maternal HBV infection and hepatitis flares, leading to serious and lethal complications. Hepatitis flares are common especially postpartum, and they are unpredictable and unpreventable with antiviral treatment. Evidence on the association between HBsAg seropositivity with gestational diabetes mellitus, preterm birth, increased foetal growth, and reduced pregnancy hypertensive disorders is stronger than other adverse pregnancy outcomes. Baseline assessment of liver function, and viral markers and activity, can delineate the truly high-risk pregnancies for close monitoring.     

NLRP3 inflammasome: a new therapeutic target for high-risk reproductive disorders?

The NOD-like receptor protein 3 (NLRP3) inflammasome is a key regulator of the host''s immune response, and many immune and metabolic disorders are linked to its activation. This review aimed to investigate and clarify the relationship between this inflammasome and high-risk reproductive disorders. Papers cited here were retrieved from PubMed up to August 2020 using the keywords “NLRP3” or “NALP3”, “caspase-1”, “endometriosis”, “gestational diabetes”, “interleukin (IL)-18”, “IL-1β”, “pre-eclampsia (PE)”, “preterm birth”, “polycystic ovarian syndrome (PCOS)”, “recurrent spontaneous abortion (RSA)”, and combinations of these terms. The results show that NLRP3 inflammasome is associated with various high-risk reproductive disorders and many inflammatory factors are secreted during its activation, such as IL-1β induced during the development of endometriosis. PCOS is also associated with activation of the NLRP3 inflammasome, especially in overweight patients. It also participates in the pathogenesis of RSA and is activated in fetal membranes before preterm birth. The placentas of pregnant women with PE show higher expression of the NLRP3 inflammasome, and gestational diabetes mellitus occurs simultaneously with its activation. Current evidence suggest that the NLRP3 inflammasome plays an important role in female reproductive disorders. New treatment and management methods targeting it might help reduce the incidence of such disorders and improve neonatal outcomes.     

早发型重度子痫前期分娩前后CD28/CTLA-4的相关研究

目的:探讨白细胞分化抗原28/细胞毒性T淋巴细胞相关抗原4(CD28/CTLA-4)与早发型重度子痫前期发病的关系。方法:采用流式细胞技术分别测定30例早发型重度子痫前期患者分娩前后的CD28、CTLA-4、CD28/CTLA-4表达水平,同时测量各组受试者血压及肝肾功能。结果:早发型重度子痫前期患者分娩前CD3+CD4+CTLA-4+、CD3+CD8+CTLA-4+高于分娩后,CD3+CD4+CD28+/CD3+CD4+CTLA-4+、CD3+CD8+CD28+/CD3+CD8+CTLA-4+低于分娩后,差异有统计学意义(均P0.05)。CD3+CD4+CD28+/CD3+CD4+CTLA-4+、CD3+CD8+CD28/CD3+CD8+CTLA-4+两者无直线相关性(r=-0.037,P=0.844)。结论:早发型重度子痫前期患者分娩后较分娩前CTLA-4的表达下降,CD28/CTLA-4上升,可能提示CD28/CTLA-4免疫偏移与子痫前期的发生有关。     

血清补体C1q肿瘤坏死因子相关蛋白3、亲环素A与子痫前期患者脂代谢异常的相关性研究

目的探讨血清补体C1q肿瘤坏死因子相关蛋白(CTRP)-3、亲环素A(CyPA)与子痫前期(PE)患者脂代谢异常的相关性。 方法选取2017年1月至2018年6月,青海大学附属医院产科收治的98例PE患者为研究对象。根据PE严重程度,将其分为重度PE组(n＝48)与轻度PE组(n＝50)。同时采用随机数字表法,选取同期于本院进行定期产前检查的50例健康孕妇作为对照,纳入对照组。采用酶联免疫吸附法,检测3组受试者的血清CTRP-3、CyPA水平。采用全自动生化分析仪,检测3组受试者的血清总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)与低密度脂蛋白胆固醇(LDL-C)水平。采用单因素方差分析,对3组受试者的人体质量指数(BMI)、收缩压、舒张压及血清TG、TC、LDL-C、HDL-C、CTRP-3、CyPA水平进行总体比较;然后,再采用最小显著性差异(LSD)法,进一步两两比较。PE患者血清CTRP-3、CyPA水平与其血清TG、TC、LDL-C、HDL-C水平的相关性,采用Pearson相关性分析。PE患者血清CTRP-3、CyPA水平与其脂代谢指标的多因素分析,采用多重线性回归法。本研究遵循的程序符合2013年修订的《世界医学协会赫尔辛基宣言》要求。3组受试者年龄、孕龄分别比较,差异均无统计学意义(P>0.05)。 结果①3组受试者BMI、收缩压、舒张压及血清TG、TC、LDL-C、HDL-C、CTRP-3、CyPA水平分别总体比较,差异均有统计学意义(F＝5.138、6.742、7.012、7.436、6.538、6.715、7.213、27.659、7.704,P<0.05)。对其进一步进行两两比较的结果显示,重度PE组和轻度PE组受试者BMI、收缩压、舒张压及血清TG、TC、LDL-C、CyPA水平,均分别显著高于对照组,并且差异均有统计学意义(重度PE组vs对照组：LSD-t＝7.156、13.864、8.664、14.264、6.837、13.875、28.185,P<0.001;轻度PE组vs对照组：LSD-t＝5.875、11.673、7.148、10.643、4.184、11.684、23.686,P<0.001);而血清HDL-C、CTRP-3水平,则均分别显著低于对照组,并且差异亦均有统计学意义(重度PE组vs对照组：LSD-t＝12.864、44.378,P<0.001;轻度PE组vs对照组：LSD-t＝9.547、31.684,P<0.001)。重度PE组受试者的BMI、收缩压、舒张压及血清TG、TC、LDL-C、CyPA水平,均显著高于轻度PE组,并且差异均有统计学意义(LSD-t＝4.738、P<0.001,LSD-t＝9.814、P<0.001,LSD-t＝4.864、P<0.001,LSD-t＝2.326、P＝0.042,LSD-t＝2.563、P＝0.028,LSD-t＝2.713、P＝0.022,LSD-t＝6.145、P<0.001);而血清HDL-C、CTRP-3水平,则均显著低于轻度PE组,差异亦均有统计学意义(LSD-t＝6.258、16.386,P<0.001)。②PE患者的血清CTRP-3水平与其血清TG、TC、LDL-C水平,均分别呈负相关关系(r＝－0.546、－0.573、－0.601,P<0.001),而其血清CTRP-3水平与血清HDL-C水平,则呈正相关关系(r＝0.531,P<0.001)。PE患者的血清CyPA水平与其血清TG、TC、LDL-C水平,均分别呈正相关关系(r＝0.612、0.637、0.552,P<0.001),而其血清CyPA水平与血清HDL-C水平,则呈负相关关系(r＝－0.514,P<0.001)。③血清TG、TC、LDL-C、HDL-C水平,均分别为PE患者血清CTRP-3、CyPA水平的独立影响因素(血清CTRP-3水平：t＝4.427、P<0.001,t＝3.675、P<0.001,t＝2.328、P＝0.020,t＝4.576、P<0.001;血清CyPA水平：t＝2.788、P＝0.005,t＝3.332、P＝0.001,t＝2.429、P＝0.015,t＝2.140、P＝0.032)。 结论PE患者血清CTRP-3水平较正常值降低、CyPA水平较正常值升高。CTRP-3、CyPA水平与其脂代谢异常具有相关关系,可能参与PE的发生、发展过程。     

肿瘤坏死因子α调控MPO的分泌在子痫前期发病中的作用

子痫前期(PE)是引起全球孕产妇及新生儿发病率和死亡率升高的妊娠特发性疾病。目前其病因尚未完全明确,单一生物标志物也很难预测其变化。PE患者经积极治疗病情无好转或进行性恶化时,终止妊娠是其唯一有效的治疗措施。学者认为血管内皮细胞损伤是PE的主要发病机制。近年研究发现,PE患者血浆中肿瘤坏死因子α(TNF-α)的异常表达参与疾病的发生和发展。TNF-α与相关受体结合后,可活化丝裂原活化蛋白激酶(MAPK)信号通路导致下游靶蛋白髓过氧化物酶(MPO)水平上调。中性粒细胞过度活化后释放MPO,其表达水平增高是血管内皮细胞损伤的关键因素。综述TNF-α调控MPO的相关机制在PE发病中作用的研究进展。     

妊娠期高血压和子痫前期对肾脏功能的长期影响

目的:评估妊娠期高血压(GH)和子痫前期(PE)对肾脏功能的长期影响。方法:回顾性分析本院2013年1月—2015年8月3 583例GH(GH组)、811例PE(PE组)和10 457例健康(对照组)初产妇的临床资料。随访2年,比较3组孕妇慢性肾脏病(CKD)、肾病入院等情况。结果:GH和PE初产孕妇的CKD发生率分别为5.2%(188/3 583)和7.5%(61/811),对照组CKD发生率为3.9%(405/10 457)。校正前PE组CKD危险比为2.02(95%CI:1.53~2.67),GH组为1.37(95%CI:1.15~1.64);校正年龄、产龄、体质量指数(BMI)、文化程度和吸烟状况后,CKD危险比分别为1.92(95%CI:1.45~2.56)和1.36(95%CI:1.14~1.63)。Logistic回归分析显示,PE组CKD危险比高于GH组,且两组CKD危险比、肾病入院危险比皆高于对照组(危险比为1)。结论:GH和PE增加了初产孕妇的CKD风险,发病早于血压正常初产孕妇。     

Salt,aldosterone and extrarenal Na+ - sensitive responses in pregnancy

Outside of pregnancy excessive salt consumption is known to be harmful being linked to increased blood pressure and cardiovascular disease. However, pregnancy represents a major change to a woman's physiology resulting in an intimate adaptation to environmental conditions. It is now becoming apparent that salt is essential for a number of these changes during pregnancy including haematological, cardiac adaptations as well as directly influencing placental development and the uteroplacental immune environment. The present review discusses the important role that salt has during normal pregnancy and evidence will also be presented to show how the placenta may act as a salt sensing organ temporarily, yet substantially regulating maternal blood pressure.