高血糖致胎鼠神经管畸形的发生机理及牛磺酸拮抗作用的研究

目的　探讨高血糖、农药敌枯双的胎鼠致畸机理及牛磺酸的拮抗作用。方法　采用皮下注射高渗葡萄糖的方法致孕鼠高血糖 (高血糖组 )、给孕鼠饮用敌枯双 (敌枯双组 )、给孕鼠饮用牛磺酸 (牛磺酸拮抗组 )及其各自对照组 ,RT PCR及免疫组化方法检测各组胚胎组织中Pax3及Cx43基因的mRNA及其蛋白的表达。结果　高血糖组孕鼠血糖为 (13 4± 0 8)mmol/L ,吸收胎发生率为9 6%、死胎发生率为 4 3 %及神经管缺陷畸形发生率为 8 6% ,Pax3mRNA表达降低 (0 97± 0 2 0 ) ,Pax3蛋白也降低 (0 11± 0 0 2 ) ,Cx43mRNA过度表达 (7 0 5± 1 63 ) ,Cx43蛋白表达升高 (0 94±0 0 5) ;敌枯双组孕鼠Pax3mRNA的表达与高血糖组比较 ,无明显改变。但Cx43有过度表达 (Cx43mRNA 6 96± 0 73 ,Cx43蛋白 0 92± 0 12 ) ,与高血糖组比较 ,差异有极显著性 (P <0 0 1) ;牛磺酸组孕鼠的死胎、神经管缺陷畸形发生率均为 0 % ,吸收胎发生率为 2 8% ,Pax3及Cx43mRNA和蛋白均无过度表达现象。结论　 (1)高血糖可能是糖尿病致畸的主要原因 ,其致畸机理可能是诱发Pax3基因突变 ,继而使Cx43基因过度表达 ;(2 )敌枯双的致畸作用可能是通过诱导Cx43基因过度表达而造成的 ;(3 )牛磺酸可通过改善Pax3及Cx43基因的表达而拮抗高血糖及敌枯     

间隙连接蛋白43的磷酸化调节在卵巢上皮性癌化疗耐药中的作用

目的 通过检测卵巢上皮性癌(卵巢癌)间隙连接蛋白43(Cx43)、非磷酸化Cx43及蛋白激酶C(PKC)的表达,探讨Cx43的磷酸化调节在卵巢癌化疗耐药中的作用.方法 采用免疫组化法检测29例化疗敏感(化疗敏感组)和28例化疗耐药(化疗耐药组)卵巢癌患者癌组织中以及PKC抑制剂--星孢菌素处理后的卵巢癌顺铂耐药细胞株SKOV3/DDP细胞中Cx43、非磷酸化Cx43及PKC蛋白的表达,并采用三磷酸腺苷-生物荧光肿瘤药敏实验(ATP-TCA)检测SKOV3/DDP细胞对化疗药物的敏感性.结果 (1)免疫组化法检测显示,化疗耐药组Cx43和非磷酸化Cx43蛋白的阳性表达率(分别为54%和14%)明显低于化疗敏感组(分别为83%和59%,P<0.05);化疗耐药组PKC蛋白的阳性表达率明显高于化疗敏感组(分别为64%和31%,P<0.05).卵巢癌组织中,PKC蛋白的阳性表达率与Cx43、非磷酸化Cx43蛋白的阳性表达率呈明显负相关关系(r=-0.626和-0.714,P<0.05).(2)免疫组化法检测显示,星孢菌素处理后SKOV3/DDP细胞中PKC蛋白的表达强度减弱,Cx43及非磷酸化Cx43蛋白的表达强度增强,随着星孢菌素处理时间的延长,Cx43蛋白的表达强度进一步增强.(3)ATP-TCA检测显示,体外培养的SKOV3/DDP细胞对紫杉醇和顺铂均耐药;紫杉醇和顺铂分别联合星孢菌素处理后细胞敏感度增加,其中联合低浓度(1×10-8 mol/L)星孢菌素者为中度敏感.联合高浓度(1×10-7 moL/L)星孢菌素者为高度敏感.结论 PKC通过对Cx43的磷酸化作用导致Cx43蛋白的表达下降,降低卵巢癌对化疗药物的敏感性,这种效应可以被星孢菌素逆转.     

免疫性卵巢早衰小鼠卵巢组织中Cx43、Bcl-2表达的研究

目的:检测免疫性卵巢早衰(POF)小鼠卵巢组织中缝隙链接蛋白43(Cx43)和B细胞淋巴瘤-2(Bcl-2)的m RNA及蛋白水平,以探讨其在免疫性POF发病中的作用。方法:建立免疫性POF小鼠模型并选择同期佐剂对照组及正常对照组,分别于2周、4周、6周观察各组小鼠双侧卵巢组织学变化。ELISA法测定各组小鼠血清FSH水平。免疫组化法检测各组小鼠卵巢组织中Cx43和Bcl-2蛋白相对表达量,PCR法检测Cx43和Bcl-2 m RNA水平。结果:POF组4周及6周Cx43蛋白、Bcl-2蛋白相对表达量显著低于正常对照组和佐剂对照组(P0.05);POF组4周及6周Cx43蛋白、Bcl-2蛋白相对表达量较POF组2周降低(P0.05)。POF组4周及6周Cx43 m RNA、Bcl-2 m RNA表达水平显著低于正常对照组佐剂对照组(P0.05);POF组4周及6周Cx43 m RNA、Bcl-2 m RNA表达水平较POF组2周降低(P0.05)。结论:在免疫性POF小鼠卵巢组织中Cx43和Bcl-2蛋白及m RNA表达均下调,可能与在免疫性POF的发生发展有关。     

子宫平滑肌激活蛋白-1及间隙连接蛋白43在妊娠期的表达与分娩发动和早产的关系

目的　探讨激活蛋白-1(Activator protein-1,AP-1)、间隙连接蛋白43(connexin43,Cx43)在足月产和早产子宫平滑肌中的表达情况及其相关性. 方法　应用免疫组化法检测15例足月未临产、15例足月临产、10例早产临产产妇的子宫平滑肌中AP-1的两个亚单位c-Jun、c-Fos蛋白及Cx43的表达情况. 结果 (1)Cx43免疫组化积分在早产临产组(4.204±0.42)及足月临产组(4.33±0.51)表达水平显著高于足月未临产组(3.15±0.41)(P<0.01).(2)c-Jun蛋白在早产临产组、足月临产组、足月未临产组标记指数分别为(52.34±4.18)%、(45.25±5.24)%、(34.14±4.26)%,三组两两比较差异均有统计学意义(P<0.01).(3)c-Fos蛋白在早产临产组、足月临产组、足月未临产组标记指数分别为(53.48±4.36)%、(43.32±6.21)%、(31.29±3.34)%,三组两两比较差异均有统计学意义(P<0.01).(4)妊娠子宫平滑肌中Cx43表达与c-Jun、c-Fos蛋白表达呈正相关关系,(r=0.65、0.63,P<0.01). 结论 Cx43在分娩发动中发挥着重要的作用.妊娠子宫平滑肌中Cx43的表达水平与AP-1表达有一定的相关性.     

ATRA调节人异位子宫内膜间质细胞GJIC Connexin基因、蛋白的作用及意义

目的:探讨全反式维甲酸(ATRA)对人异位子宫内膜间质细胞间隙连接细胞间通讯(GJIC)、connexin基因、蛋白的调节作用及意义。方法:取24例子宫内膜异位症患者卵巢处异位内膜标本,分离纯化得到间质细胞,分别用0.1mmol/L、1mmol/L、10mmol/LATRA处理24h、48h、72h、96h、120h,同时设置空白对照组,采用荧光漂白后恢复技术检测异位内膜间质细胞的GJIC功能,并检测与GJIC功能密切相关的Cx43、Cx26、Cx32的基因及蛋白表达。结果:ATRA处理72h内,1mmol/L、10mmol/L组的异位内膜间质细胞荧光恢复功能明显增强;0.1mmol/LATRA组的异位内膜间质细胞荧光恢复功能无明显变化。未经ATRA处理的异位内膜间质细胞中无Cx43、Cx26、Cx32的mRNA及蛋白表达;经1mmol/LATRA处理后,异位内膜间质细胞中检测到Cx43mRNA和蛋白表达,但未见Cx26、Cx32的mRNA及蛋白表达。结论:ATRA能选择性地诱导Cx43基因及蛋白表达,从而有效上调异位内膜间质细胞的GJIC功能;ATRA可能是治疗子宫内膜异位症的潜在药物。     

卵巢癌自杀基因治疗的旁观者效应及其与间隙连接蛋白43表达的关系

目的 探讨单纯疱疹病毒－胸苷激酶／更昔洛韦（HSV－TK／GCV）在卵巢癌治疗中的旁观者效应及其与间隙连接蛋白（Cx)43表达的关系,同时观察全反式维甲酸（RA）对两者关系的影响。方法 四甲基偶氮唑蓝（MTT）法比较经HSV－TK／GCV治疗及RA作用前后卵巢癌细胞株OVCAR3、CAOV3细胞旁观者效应的强弱;采用流式细胞仪,蛋白质免疫印迹法（Western Blot)、间接免疫荧光染色检测两卵巢癌细胞株RA作用前后Cx43的表达,Cx43的表达以平均荧光强度表示。结果 （1）HSV－TK／GCV对OVCAR3细胞产生较明显的旁观者效应,而对CAOV3细胞旁观者效应弱,两者比较,差异有显著性（P＜0．05）。（2）RA对OVCAR3细胞的旁观者效应有增强作用（P＜0．05）,但不影响CAOV3细胞的旁观者效应（P＞0．05）。（3）流式细胞仪检测提示,OVCAR3细胞中Cx43的表达为4．45,而CAOV3细胞中Cx43的表达为0．89,两者比较,差异有显著性（P＜0．05）;Western Blot、间接免疫荧光染色检测结果也表明,OVCAR3细胞有Cx43的表达,且定位于细胞膜,而CAOV3细胞中无Cx43的表达。（4）RA作用后,Western Blot、间接免疫荧光染色检测均显示,两卵巢癌细胞株的Cx43表达增加;流式细胞仪检测提示,细胞中Cx43表达均明显增加,OVCAR3细胞由4．45增至9．83,CAOV3细胞由0．89增至3．15（P均＜0．05）,Cx43仍定位于OVCAR3的细胞膜和CAOV3的细胞浆。结论 卵巢癌HSV－TK／GCV治疗的旁观者效应与其Cx43表达以及定位有关,增强细胞膜Cx43表达,将增强卵巢癌HSV－TK／GCV的旁观者效应,提高其疗效。     

子宫结合带超微结构及间隙连接蛋白43的表达变化与子宫腺肌病发病的关系

目的 探讨子宫结合带的超微结构特点及间隙连接蛋白43(Cx43)在子宫结合带中的表达变化与子宫腺肌病发病的关系.方法 收集2008年11月至2009年11月在内蒙古医学院附属医院妇科住院的因子宫腺肌病行子宫全或次全切除术者30例为观察组(其中子宫内膜为增生期14例,分泌期16例),选择同期因宫颈上皮内瘤变(CIN)Ⅲ等行子宫全切除术者30例为对照组(子宫内膜为增生期、分泌期各15例).采用链霉素亲和素-生物素-过氧化物酶复合物(SABC)免疫组化法检测Cx43蛋白在子宫腺肌病患者子宫结合带中的表达水平,以吸光度(A)值表示;透视电镜观察两组中无诊断性刮宫(诊刮)史、剖宫产史、子宫手术史者(各4例)的子宫在位内膜、子宫结合带以及子宫肌层外1/3的超微结构特点.结果 (1)Cx43蛋白的表达:观察组增生期及分泌期子宫结合带中Cx43蛋白表达水平分别为0.133±0.018、0.137±0.021,对照组分别为0.154±0.016、0.141±0.018,两组同一期别子宫内膜比较,差异均有统计学意义(P＜0.05),但各组内增生期与分泌期子宫结合带中Cx43蛋白表达水平比较,差异无统计学意义(P＞0.05);观察组的在位内膜中增生期及分泌期Cx43蛋白表达水平(0.067±0.017,0.062±0142)低于对照组(0.094±0.005,0.080±0.005),差异也均有统计学意义(P＜0.05),但各组内增生期与分泌期比较,差异无统计学意义(P＜0.05);观察组和对照组增生期外肌层Cx43蛋白表达分别为0.184±0.022、0.188±0.028,差异无统计学意义(P＞0.05),分泌期外肌层Cx43蛋白表达分别为0.178±0.022、0.191±0.025,差异也无统计学意义(P＞0.05).(2)形态学变化:观察组子宫结合带平滑肌细胞核面积[(24.3±1.6)μm2]比对照组[(21.8±2.0)μm2]明显增加,差异有统计学意义(P＜0.01).细胞膜致密斑明显增长[(1.07±0.17)、(0.71±0.07)μm],差异也有统计学意义(P＜0.01);观察组子宫结合带肌细胞小凹结构减少,细胞增生肥大,排列紊乱,核表面呈圆齿状不规则外形,核染色质边集,异染色质多,细肌丝较少而中间丝较多,线粒体数量增加、体积增大、空泡化明显,粗面内质网扩张,高尔基体增加,肥大细胞与肌细胞紧密相邻;在位内膜的腺上皮细胞间呈桥粒连接,且表面绒毛增粗、致密.以上特点在观察组的外肌层也可见,但没有子宫结合带显著.结论 子宫结合带中超微结构的变化和Cx43蛋白的表达下调可能与子宫腺肌病的发病有关.     

子宫胎盘缺血对胎鼠体重及神经系统发育影响的研究

目的　探讨不同孕龄孕鼠子宫、胎盘缺血对胎鼠体重及神经系统发育的影响。方法利用子宫动脉钳夹法对妊娠 13d(缺血 1组 )及妊娠 17d(缺血 2组 )孕鼠实施单侧子宫动脉缺血手术 ,制成孕鼠子宫动脉缺血模型。缺血组孕鼠的另一侧子宫动脉不钳夹为自身对照 ,相应为对照 1组和对照 2组。比较缺血组孕鼠子宫动脉钳夹缺血侧 ,与自身对照组孕鼠子宫动脉不钳夹侧 (无缺血侧 )的胎鼠体重、脑重及脑组织生长相关蛋白 4 3(GAP 4 3)mRNA的表达。结果　 ( 1)缺血 1组胎鼠体重、脑重分别为 3 2 g和 0 16 g,显著低于对照 1组的 3 6g和 0 18g(P <0 0 1,P <0 0 1) ;缺血 2组的胎鼠体重、脑重分别为 3 1g和 0 16 g ,也显著低于对照 2组的 3 7g和 0 17g(P <0 0 1,P <0 0 5 )。 ( 2 )缺血 1组和对照 1组胎鼠脑组织GAP 4 3mRNA的表达分别为 1 10和 1 12 ,两组比较 ,差异无显著性(P >0 0 5 ) ;缺血 2组与对照 2组胎鼠脑组织GAP 4 3mRNA的表达分别为 1 0 6和 1 2 1,两组比较 ,差异有极显著性 (P <0 0 1)。结论　不同孕龄孕鼠子宫胎盘缺血均会显著抑制胎鼠的生长发育 ;妊娠晚期宫内缺血使胎脑组织GAP 4 3mRNA的表达显著减少 ,可对胎鼠的神经系统发育产生影响。     

孕中晚期不同剂量邻苯二甲酸二(2-乙基己基)酯暴露对胎鼠生长发育的影响

目的:探讨孕中、晚期不同剂量邻苯二甲酸二(2-乙基己基)酯(DEHP)暴露对孕鼠妊娠结局及胎鼠生长发育的影响。方法:将40只雌性Wistar大鼠随机分为4组:对照组(玉米油)、低剂量组(100mg/kg)、中剂量组(500mg/kg)和高剂量组(1000mg/kg)。妊娠11日起每天给予DEHP灌胃,妊娠第19日处死孕鼠。观察DEHP对孕鼠的一般情况及其对妊娠结局的影响。记录胎盘质量、活胎数、畸胎数、胎鼠体重、身长、尾长及脏器系数,明确DEHP对胎鼠生长发育的不良作用。结果:各组孕鼠的一般状况良好,中、高剂量组胎盘发生明显病理改变。与对照组相比,中剂量和高剂量染毒组的活胎数、畸胎数、胎鼠体重、身长、尾长及脏器系数比较,差异均有统计学意义(P0.05)。结论:妊娠中晚期DEHP暴露可影响胎盘及胚胎发育,使活胎数降低,胎儿发育不良、胎儿畸形数增加,导致不良妊娠结局。     

维甲酸对人子宫颈癌细胞系HeLa细胞间隙连接蛋白转导途径调控作用的研究

目的：探讨维甲酸对人子宫颈癌细胞系HeLa细胞间隙连接蛋白（Cx）43信号转导途径的调控作用。方法：应用特异性钙指示剂（Fluo-3 AM)在激光扫描共聚焦显微镜下动态观察维甲酸作用后的细胞质内信号转导分子游离钙的分布及强度变化。采用流式细胞仪、结合蛋白印迹技术分析，检测外源信号分子对Cx43的表达以及蛋白酪氨酸磷酸化状态的影响。结果：HeLa细胞内游离钙经维甲酸作用后明显超载，细胞内游离钙浓度（[Ca^2 ]i)由静息状态下的35.73μmol/L上升至58.16μmol/L。流式细胞仪分析，Cx43阳性细胞表达率由1.9%上升至26.3%。蛋白印迹技术分析，HeLa细胞出现Cx43酪氨酸磷酸化。结论：维甲酸对HeLa细胞Cx43信号转导途径的调控是在细胞质内游离钙的参与下，使Cx43阳性细胞表达率上升，并在酪氨酸位点出现明显的磷酸化作用下实现的。     

Distribution of neural tube defects as a function of maternal weight: no apparent correlation.

OBJECTIVES: Maternal nutritional deficiency is an important predisposing factor to congenital neural tube defects (NTDs). It was hypothesized that obese women may have an increased risk for NTDs. The aim of the present study was to address this question in a large cohort. METHODS: A total of 72,915 consecutive cases of biochemical screening that had documented maternal weights and pregnancy outcomes were identified from the Quest Diagnostic Laboratories database. Patients were divided into five ranges of maternal weights, and the incidence of NTDs was calculated for each group. Based on the different definitions of maternal overweight, the data were also analyzed based on 2 groups only, obese and nonobese, using three cutoff points. RESULTS: Seventy-nine pregnancies were complicated by NTDs (incidence of 1.08 per 1,000 pregnancies). Differences between maternal weights ranges were not found to be statistically significant (chi2 = 5.997, p = 0.19, power = 0.99). Differences between obese and nonobese mothers were not found to be statistically significant for all three analyses as well. CONCLUSIONS: Our present results do not support an association between maternal obesity and NTDs.     

A study of the value of measuring maternal serum alpha-fetoprotein for the antenatal diagnosis of neural tube defects

Summary Two neighbouring centres, both located in an area where the prevalence of neural tube defects (NTDs) is low, were compared to determine if there was any advantage in their differing policies as regard the antenatal detection of NTDs. At both centres routine ultrasound examinations were performed at 16–18 weeks gestation but at Hospital A serum alpha-fetoprotein (AFP) was measured at 16 weeks gestation. The prevalence of NTDs was 1.3 per 1,000 births at Hospital A and 1.7 per 1,000 births at Hospital B. The detection of anencephaly at both hospitals was 100%, however, only 43% of spina bifidas were detected at Hospital A compared with 60% at Hospital B. These results, the loss of two fetuses following amniocentesis at Hospital A and the lower detection rate for NTDs at the hospital employing AFP measurement are discussed.     

Awareness of the use of folic acid to prevent neural tube defects in a Mediterranean area

OBJECTIVES: The risk of neural tube defects (NTDs) is decreased in women who take folic acid during the periconceptional period. The main objective of our study was to evaluate the awareness of the need for folic acid supplementation and also the actual intake during the periconceptional period to prevent neural tube defects in a Mediterranean area. STUDY DESIGN: A retrospective study was performed from 1 July to 30 November 2000. One thousand consecutive women who delivered in our hospital were interviewed during the immediate postpartum period about their knowledge of neural tube defects and folic acid intake before and during pregnancy. RESULTS: Most women (85.7%) referred not having been specifically informed about the need to take folic acid to prevent neural tube defects although approximately half of the women (50.6%) were in fact, aware of the need for folic acid intake. Eight percent (8.1%) of the women took folic acid before conception but only 6.9% did so during the effective period from 4 weeks before conception to 4 weeks after conception. Logistic regression analysis showed that awareness of the need to take folic acid together with having had preconceptional counselling and knowledge of NTDs were the strongest variables related to the fact of having taken folic acid during the correct period. CONCLUSIONS: Although the population is aware of the need to take folic acid, the real impact of the present recommendations is almost negligible. Information in primary care and preconceptional counselling to specifically inform patients about the need to take folic acid to prevent NTDs seem to be crucial to improve the final intake of folic acid during the protective period.     

MTHFR 677C-->T and 1298A-->C polymorphisms: evaluation of maternal genotypic risk and association with level of neural tube defect

BACKGROUND: Neural tube defects (NTDs) are common birth defects (1 in 1,000) leading to significant morbidity and mortality. Periconceptional folic acid supplementation helps in prevention of 70% of NTDs. Recently, polymorphisms in genes encoding enzymes of the folate pathway have been implicated in causation of NTDs. Since the closure of neural tube occurs at multiple sites, the etiology of defect at different sites may be different - which explains the failure of folic acid supplementation to prevent all NTDs. METHODS: Molecular analysis of methylenetetrahydrofolate reductase polymorphisms was carried out using polymerase chain reaction and restriction enzyme digestion. We studied the association of these polymorphisms in mothers with a previous child with NTD and further refined the risk by stratification based on level of defect. RESULTS: The frequency of 677C-->T homozygotes was higher in mothers with a previous child with NTD than the controls (OR = 1.6 (0.38-6.7), 95% CI, p = 0.72) but the difference was statistically insignificant. There was a significant difference in frequency of T alleles among mothers with a previous child with a 'lower' type of defect compared to controls (OR = 2.15 (1.13-4.1), 95% CI, p = 0.02). We did not find any significant association of 1298A-->C polymorphism with the level of NTDs. CONCLUSIONS: We conclude that in the North Indian population, the 677C-->T allele of the MTHFR gene may be associated with the occurrence of a lower type of NTD. This points towards the differential role of thermolabile MTHFR at different sites of neural tube closure.     

Postmortem evaluation of 220 prenatally diagnosed fetuses with neural tube defects: detection of associated anomalies in a Turkish population

OBJECTIVES: The aim of this study is to represent the distribution of disorders resulting from neural tube defects (NTDs). MATERIALS AND METHODS: This study was conducted on 220 prenatally diagnosed cases with NTDs. Fetuses were evaluated by physical examination, anthropometric measurements, X-rays, and photographs after termination of pregnancy. Chromosome analysis and autopsy were performed for 37 fetuses (16.8%) with additional malformations. RESULTS: In 29 out of 37 fetuses (78.4%), additional malformations were detected by prenatal ultrasonography, whereas in eight cases postmortem evaluation produced additional findings that were not detected prenatally. Fourteen of 37 (37.8%) and 65 of 220 (29.5%) fetuses had clubfoot, which was mostly secondary to NTDs. There was no difference in sex distribution between isolated NTDs and the group with additional abnormalities and among the groups anencephaly and anencephaly + anomaly, encephalocele and encephalocele + anomaly, spina bifida and spina bifida + anomaly. There was only one case, a female fetus, with iniencephaly in this group. Anencephaly was more frequent in cases with isolated NTDs (48.1%) than in those with additional anomalies (27%). There was no difference for other groups of NTDs. The most frequent disorder was vertebral segmentation defects, which were detected in 11 out of 37 cases (29.7%). CONCLUSIONS: Evaluation of associated malformations and confirmation of ultrasound findings can be performed by postmortem examination and simple X-ray studies for exact diagnosis, which strongly affects decisions on further pregnancies as well as genetic counseling. This method is straightforward, inexpensive and effective.     

Pathogenesis and genetics of neural tube defects

After congenital heart defects neural tube defects (NTDs) is the second most prevalent congenital malformation among birth defects. The average rate of isolated NTDs is 1.4-2.0 per 1000 live births worldwide. The etiology of isolated (nonsyndromic) NTDs is believed to be the result of a combination of genetic predisposition and environmental factors. Over 80 genes believed to be engaged in the neurulations have been identified during the investigation and research of the mouse models. Despite exhaustive research efforts, now spanning several decades, little is known about the actual genetic mechanisms governing the primary events involved in neural tube closure (NTC).     

Homocysteine metabolism in families from southern Italy with neural tube defects: role of genetic and nutritional determinants

OBJECTIVE: To evaluate the role of different polymorphic gene variants involved in homocysteine metabolism and plasma levels of homocysteine, folate and vitamin B12 in families from southern Italy with neural tube defects (NTDs). METHODS: Eighteen fathers, 15 NTD children and 60 women who had conceived NTD foetuses were investigated. A group of 100 adults and 43 apparently healthy children was used as control. At the time of blood draw, none were taking vitamin pills or nutritional supplements. RESULTS: Among controls, 79 (55.2%) were heterozygous for C677T MTHFR variant and 26 (18.2%) were TT homozygous. Among the cases, 35 (61.4%) out of 57 mothers and 7 (38.9%) out of 18 fathers carried the T allele; 12 (21.1%) mothers and 2 (11.1%) fathers had the TT genotype. Four (26.7%) out of 15 probands were TT homozygous and 11 (73.3%) were heterozygous (Fisher exact test p = 0.025). No significant difference between groups was observed for the 1298C MTHFR variant and CBS haplotypes. Median homocysteine in NTD children was significantly higher (10.0 micromol/L) than that of controls (median 4.5 micromol/L, Mann-Whitney p < 0.05). Folate and B12 were not different among groups. CONCLUSIONS: The T677 MTHFR allele is significantly associated with the occurrence of NTDs; no significant association has been observed with other genetic determinants analysed. Homocysteine levels in children with NTDs are significantly higher than those of the paediatric population from the same geographical area.     

Periconceptional factors affect the risk of neural tube defects in offspring: a hospital-based case-control study in China

Abstract

Objective: To explore the periconceptional factors affecting the risk of neural tube defects (NTDs), we carried out a hospital-based case-control study in China.

Methods: A 1:1 matched case-control study was conducted. With self-designed questionnaires, we solicited relevant information from 459 case mothers and 459 control mothers selected in two provinces of China through face-to-face interviews. Univariate and multivariate conditional logistic regression analyses were conducted to evaluate the effect values by odds ratios (ORs) and 95% confidence intervals (95%CIs) with SAS9.1.3.software.

Results: Daily passive tobacco smoke exposure was a risk factor for total NTDs (OR?=?8.688, 95%CI?=?2.329–32.404). Diet adjustment in the first trimester (OR?=?0.061, 95%CI?=?0.014–0.274), periconceptional folic acid intake (OR?=?0.059, 95%CI?=?0.011–0.321) and health education (OR?=?0.251, 95%CI?=?0.081–0.781) were protective factors for total NTDs. Differences in factors and their effects on NTDs were found for the three subtypes of NTDs: anencephaly, spina bifida and encephalocele.

Conclusions: Daily passive tobacco smoke exposure, diet adjustment in the first trimester, periconceptional folic acid intake and health education were associated with NTDs.