膳食叶酸和MTHFR基因多态性对乳腺癌发病的影响

目的 探讨膳食叶酸摄入、5,10-亚甲基四氢叶酸还原酶(MTHFR)基因多态性联合暴露与乳腺癌发病风险的关系。方法 采用匹配病例对照研究,从2014年4月-2015年5月,序贯收集乳腺癌新发病例794例,从2015年4月～2015年6月,招募健康女性805例。采用问卷调查收集研究对象一般人口学特征、乳腺癌常见危险因素、膳食情况等信息;采用飞行时间质谱生物分析技术检测MTHFRC677T基因型;采用非条件多因素Logistic回归分析MTHFRC677T基因多态性及膳食叶酸(水果、蔬菜日摄入量)与乳腺癌发病风险的关系。结果 调整年龄、婚姻状况、主动吸烟、被动吸烟、人工流产次数、乳腺良性疾病、日均能量摄入后,结果提示水果日摄入量低增加乳腺癌发病风险(OR=1.869,95%CI〖WTBZ〗:1.494~2.337);以水果高摄入联合MTHFRC677T-〖WTBZ〗CC型为参照,水果低摄入联合CC型或CT+TT型均增加乳腺癌发病风险(ORs>1.6,95%CI〖WTBZ〗不包含1)。结论 膳食叶酸(水果)的摄入可降低乳腺癌的发病风险,但与叶酸代谢相关的MTHFR C677T基因多态性可能不独立影响乳腺癌的发病风险。     

Relationship between dietary folate intakes,maternal plasma total homocysteine and B-vitamins during pregnancy and fetal growth in Japan

Background Adequate folate status in pregnancy is important for satisfactory pregnancy outcome. Aim of the Study The objective of the present study was to evaluate folate status in healthy pregnant women by assessing dietary folate intakes and measuring changes in folate-related biomarkers including plasma tHcy, serum vitamin B₁₂ (B₁₂), and serum and RBC folate concentrations in each trimester and to examine their relation to fetal growth. Methods From 94 pregnant women, 3-day-dietary records were obtained and blood was collected for plasma total homocysteine (tHcy), serum B₁₂, and serum and red-blood cell (RBC) folate measurements. Infant anthropometric measurements were made immediately after birth. Results Average folate intake was less than 300 μg/day with a mean energy intake of about 1800 kcal. Mean serum and RBC folate concentrations declined significantly during gestation (p < 0.05). Mean serum B₁₂ also significantly decreased (p < 0.01), whereas plasma tHcy increased from 5.1 in the first trimester to 5.9 μmol/l in the third trimester (p < 0.01). Multiple regression analyses, after controlling for maternal age, parity and pre-pregnancy body-mass index indicated that a 1.0 μmol/l increase in plasma tHcy in the third trimester corresponded to a 151 g decrease in birth weight (p < 0.01). Neither B₁₂ nor folate concentrations in all three trimesters showed any significant associations with birthweight. Plasma pyridoxal-5′-phosphate concentrations were markedly low, and were consistent with low intake of vitamin B₆ in our population. Conclusion Our data suggest that higher plasma tHcy in the third trimester is a predictor of lower birth weight. In general, the dietary intake of B-vitamins and energy may be inadequate in our population, suggesting intervention is necessary.     

上海地区孕妇MTHFR C677T基因多态性与血浆同型半胱氨酸水平的关联性分析

目的 了解上海市孕妇MTHFR基因型的分布情况,分析MTHFR C677T基因多态性与高同型半胱氨酸血症的关联性,为高危孕妇的遗传筛查及围产期叶酸摄入的个性化提供依据。方法 选取上海市五所社区医院2015年1月~2015年6月门诊建卡孕妇1000例,随访了解基本信息、孕期危险因素暴露及叶酸摄入情况,以基因芯片法检测MTHFR基因型,循环酶法检测血浆同型半胱氨酸。结果 上海地区孕妇MTHFR C677T基因CC型、CT型、TT型的检出频率分别为33.0%、49.2%、17.8%,等位基因C、T的频率为57.6%、42.4%,样本人群处于H-W平衡状态。血浆同型半胱氨酸浓度为11.22（9.15,13.52）μmol/L,其中911例（91.6%）正常,84例（8.4%）属轻度高同型半胱氨酸血症。经多因素logistic回归分析,CT型与TT型发生高同型半胱氨酸血症的OR值分别为2.18（95%CI：1.11~4.25）和6.26（95%CI：3.13~12.53）。结论 MTHFR基因C677T多态性与孕妇血浆同型半胱氨酸水平存在关联,携带等位基因T者可视为高危孕妇,孕期叶酸补充可适量增加。     

孕妇血清 Fol、VB12和 Hcy水平与胎儿 CHD相关性研究

目的 比较胎儿先天性心脏病（ CHD）的孕妇和正常孕妇血清叶酸（ Fol）、维生素B12（ VB12）和同型半胱氨酸（ Hcy）水平,以了解3种物质的代谢水平与胎儿CHD的关系。方法 根据有无胎儿CHD将研究对象分为病例组（ n＝46）和对照组（n＝43）。病例组为经B超诊断为孕CHD胎儿确诊的孕妇,对照组为经B超诊断胎儿发育正常的孕妇。检测89例研究对象血清标本Fol、VB12和Hcy水平,比较病例组和对照组血清Fol、VB12和Hcy水平差异。结果 病例组的Fol水平高于对照组,差异有统计学意义（t＝2．426,P＝0．017）;病例组Hcy水平高低于对照组,但差异无统计学意义（P＞0．05）。血清Fol≥44．5nmol／L的孕妇与＜38．6nmol／L的孕妇相比,胎儿CHD发生率降低36倍;Hcy的OR＝1．036（95％CI：0．807～1．329）,但并未增加胎儿CHD发生的危险性（P＞0．05）;VB12的OR＝1．007（95％CI：1．001～1．013）,增加胎儿CHD发生的危险性（P＝0．015）。 Fol和VB12对CHD的发生都有关联,差异均有统计学意义（P＝0．046,P＝0．020）,但是曲线下的面积都＜70％,用这两个指标单独进行诊断无很大价值。结论 孕妇高水平Fol是妊娠胎儿CHD的保护因素,VB12是妊娠胎儿CHD的危险因素,血清Fol和VB12联合检测对胎儿CHD的发生更有预测价值。     

MTHFR、MTRR基因多态性与多囊卵巢综合征的相关性研究

目的探讨亚甲四氢叶酸还原酶(MTHFR)、甲硫氨酸合成酶还原酶(MTRR)基因多态性与多囊卵巢综合征(PCOS)的相关性。方法应用病例对照研究,收集2018年4月-2018年8月在广东省妇幼保健院就诊的育龄期PCOS患者55例为PCOS组,选取46例月经规则、有排卵,并完成一次生育的非PCOS患者作为对照组。在PCOS组中,按HOMA稳态模型(HOMA-IR)分为两组,PCOS胰岛素抵抗(PCOS-IR)组和PCOS非胰岛素抵抗(PCOS-NIR)组,按多毛评分标准(m FG score)和血清游离雄激素指数(FAI)分为两组,高雄激素症组和非高雄激素症组,分别提取血浆,利用荧光定量PCR方法检测MTHFR基因C677T、A1298C及MTRR基因A66G的单核苷酸多态性(SNPs),同时采用化学发光法检测两组血浆维生素B12、叶酸及同型半胱氨酸(HCY)的含量。结果MTHFR基因C677T等位基因C在PCOS组分布频率高于对照组,差异有统计学意义(P<0.05),等位基因C使PCOS的风险增加2.077倍(95%CI:1.132~3.812)。677CC基因型在PCOS组的分布频率明显高于对照组,差异有统计学意义(P<0.05),野生基因型(CC)与纯合突变基因型(TT)相比,患PCOS的风险提高了4.392倍(95%CI:1.005~19.196)。两组MTHFR基因A1298C、MTRR基因A66G各基因型和等位基因频率的分布差异无统计学意义(P>0.05)。在PCOS组中,PCOS-IR组和PCOS-NIR组以及高雄激素症组和非高雄激素症组在MTHFR基因C677T、A1298C及MTRR基因A66G各基因型分布差异无统计学意义(P>0.05),MTHFR C677T、A1298C及MTRR A66G位点分布之间不存在交互作用(P>0.05)。PCOS组中HCY水平较对照组明显升高,差异有统计学意义(P<0.05),两组血清维生素B12、叶酸水平差异均无统计学意义(均P>0.05)。结论MTHFR基因C677T多态性与PCOS的发病有一定的相关性,CC基因型可增加PCOS的发生风险,但与胰岛素抵抗(IR)和高雄激素症的发生风险无关。MTHFR基因A1298C、MTRRA66G各基因型与PCOS的发生、IR及高雄激素症的发生无关,PCOS组HCY偏高。     

泸州汉族人群MTHFR基因多态性分布及育龄妇女该基因多态性与复发性流产相关性的研究

目的了解泸州市亚甲基四氢叶酸还原酶(MTHFR)基因多态性分布情况以及该单核苷酸多态性与复发性流产的相关性。方法选取2016-2018年在西南医科大学附属医院进行MTHFR基因检测的泸州汉族人群691例为研究对象,利用PCR-微阵列基因芯片法检测其C677T单核苷酸多态性,统计得出3种基因型的频率以及等位基因频率,并与全国其他地区已报道的多态性分布特征进行比较。结果泸州汉族人群CC、CT与TT基因型频率分别为39.2%、46.7%、14.0%,T等位基因频率为37.4%。其中女性T等位基因频率为38.1%,基因分布与纬度相近地区(N25°~31°)差异无统计学意义(P>0.05),与南方的海南、惠州及北方的西安、银川、赤峰、烟台人群差异有统计学意义(P<0.05)。在泸州育龄妇女中,复发性流产与MTHFR C677T基因多态性暂未发现存在直接关联。结论泸州地区汉族人群的MTHFR基因分布具有西南地区的分布特征,T等位基因频率整体呈现出随着纬度升高而升高的趋势。     

Determinants of arsenic metabolism: blood arsenic metabolites, plasma folate, cobalamin, and homocysteine concentrations in maternal-newborn pairs

BACKGROUND: In Bangladesh, tens of millions of people have been consuming waterborne arsenic for decades. The extent to which As is transported to the fetus during pregnancy has not been well characterized. OBJECTIVES: We therefore conducted a study of 101 pregnant women who gave birth in Matlab, Bangladesh. METHODS: Maternal and cord blood pairs were collected and concentrations of total As were analyzed for 101 pairs, and As metabolites for 30 pairs. Maternal urinary As metabolites and plasma folate, cobalamin, and homocysteine levels in maternal cord pairs were also measured. Household tube well-water As concentrations exceeded the World Health Organization guideline of 10 microg/L in 38% of the cases. RESULTS: We observed strong associations between maternal and cord blood concentrations of total As (r = 0.93, p < 0.0001). Maternal and cord blood arsenic metabolites (n = 30) were also strongly correlated: in dimethylarsinate (DMA) (r = 0.94, p < 0.0001), monomethylarsonate (r = 0.80, p < 0.0001), arsenite (As(+3)) (r = 0.80, p < 0.0001), and arsenate (As(+5)) (r = 0.89, p < 0.0001). Maternal homocysteine was a strong predictor of %DMA in maternal urine, maternal blood, and cord blood (beta = -6.2, p < 0.02; beta = -10.9, p < 0.04; and beta = -13.7, p < 0.04, respectively). Maternal folate was inversely associated with maternal blood As(5+) (beta = 0.56, p < 0.05), and maternal cobalamin was inversely associated with cord blood As(5+) (beta = -1.2, p < 0.01). CONCLUSIONS: We conclude that exposure to all metabolites of inorganic As occurs in the prenatal period.     

A critical evaluation of the relationship between serum vitamin B12, folate and total homocysteine with cognitive impairment in the elderly

Background Serum homocysteine increases with age and is also considered a marker for low serum vitamin B₁₂ and folate. Furthermore, raised serum total homocysteine has been associated with atrophic changes in the brain. An association between serum vitamin B₁₂/folate and cognitive impairment would be of considerable public health importance in view of the increasing numbers of elderly people. Aim To systematically review published studies on the relationship between serum vitamin B₁₂, folate and total homocysteine and cognitive function in the elderly. Design and data sources A systematic review was undertaken of published evidence in English, examining the association between low serum vitamin B₁₂/folate and raised total homocysteine with cognitive impairment (as indicated by low scores on neuropsychological testing) in subjects aged over 60 years. Sixteen electronic databases and cited articles were searched. Of 383 potential articles, six fulfilled the eligibility criteria: three case control and three cohort studies were identified. ‘The Cochrane Non‐Randomized Studies Methods Group’ guidelines were used for assessment and extraction of data from these studies. Results All three case control studies found that serum total homocysteine was significantly higher in cases when compared with controls, and there was wide variation for both serum vitamin B₁₂ and folate in both groups of participants. The relationship of serum folate and vitamin B₁₂ status with cognitive impairment was heterogeneous and one case control study reported decreasing cognitive scores with increasing serum vitamin B₁₂. In the cohort studies, although serum total homocysteine could predict the rate of decline in neuropsychological testing, the overall odds ratio/relative risk (RR) of developing cognitive impairment in relation to levels of serum B₁₂ and serum folate were not significant. Although one study reported a significant RR of developing Alzheimer's disease when both serum folate and B₁₂ levels were low. One cohort study reported an increased prevalence of Alzheimer's type dementia in subjects who had normal serum vitamin B₁₂ at baseline. Conclusion Serum total homocysteine is negatively correlated with neuropsychological tests scores. But the evidence does not support a correlation between serum vitamin B₁₂ or folate and cognitive impairment in people aged over 60 years. Hence, there is little evidence to justify treating cognitive impairment with vitamin B₁₂ or folate supplementation. This is consistent with the findings from recent systematic reviews of randomized double‐blind trials, which have not found any evidence of potential benefit of vitamin supplementation. Further research is required in order to establish whether raised serum total homocysteine is a cause or consequence of disease.     

Serum homocysteine concentration as a marker of nutritional status of healthy subjects in Crete, Greece

BACKGROUND: Dietary habits are an important determinant of serum homocysteine (tHcy), which may be a marker rather than a cause of progression of the atherosclerotic process. The aim of the present study was to evaluate the nutritional status, and to determine the serum tHcy concentrations in healthy subjects who live in rural areas of Crete, and who theoretically follow a contemporary Mediterranean-style diet. METHODS: Serum tHcy, folate, vitamin B(12), creatinine, glucose, and the lipid profile, were measured in 203 (141 men and 62 women) healthy subjects, aged 33-78 years. The major risk factors for cardiovascular disease such as age, gender, cigarette smoking, obesity were recorded and dietary data were assessed using a 3-day weighed food intake record. RESULTS: Our population had high serum tHcy, low serum folate concentrations and lower than the traditional Cretan dietary folate intake [median (range): 12.0 (3.6-44.7) micromol L(-1), 7.9 (1.9-15.5) ng mL(-1) and 241 (68-1106) microg, respectively]. Dietary intake of fibre, omega-3, and mono- or/ polyunsaturated fatty acids was also low. An inverse relation was observed between serum tHcy concentrations and serum folate (r = -0.28; P < 0.01) and vitamin B(12) levels (r = -0.33; P < 0.001). CONCLUSIONS: Nowadays, the Cretan diet has changed towards a more westernized eating pattern. Given the analytic difficulties in determining the amount of folate in food and the inverse correlation between serum tHcy and folate levels, serum tHcy concentrations may be a useful marker for nutritional status, especially folate deficiency, in healthy subjects.     

孕期化学物接触及基因多态性与先天性心脏病

目的 探讨5,10-亚甲基四氢叶酸还原酶MTHFR基因C677T多态性和孕期接触化学物与先天性心脏病的关系.方法 采用病例-对照研究设计,选择144例病例和168例对照,采用面访法和聚合酶链反应-限制性片段长度多态性分析法(PCR-RFLP)进行检测,运用多因素Logistic回归模型分析MTHFR基因C677T多态性与孕期化学物接触对先心病的作用强度和交互作用.结果 MTHFR677TT基因型发生先天性心脏病的风险是MTHFR677CT或CC基因型的3.215倍(95%CI=1.958~5.280);孕期化学物接触与子代先天性心脏病关联强度OR值为2.150(95%CI=1.041~4.442);MTHFR677TT基因型与孕期化学物接触具有正相加交互作用,交互作用的效应量(RERI)、归因交互效应百分比[AP(AB)]和纯因子间归因交互效应百分比[AP*(AB)]分别为4.938,60.23%,68.59%.结论 MTHFR基因C677T变异可与孕期接触化学物协同增加子代罹患先心病的危险性.     

母亲MTHFR 677C/T多态性和孕期状况与子代发生先天性心脏病的相关性研究

目的 探讨母亲孕期MTHFR 677C/T多态性、孕期状况在子代先天性心脏病(CHD)发生中的相互关系。方法 采用病例对照研究,调查100对CHD胎儿和无CHD胎儿生物学母亲有关人口学、孕期环境相关情况、优生认知,并检测MTHFR 677C/T基因多态性以及血清同型半胱氨酸(HCY)、叶酸、VitB12水平,进行单因素和多因素非条件logistic回归分析。结果 病例组和对照组MTHFR 677C/T基因型和等位基因频率差异无统计学意义(χ²=1.08,P=0.582;χ²=0.53,P=0.468),血清HCY水平两组差异有统计学意义(t=-8.14,P=0.000)。单因素分析,14个因素有统计学意义(P<0.05);多因素logistic逐步回归分析,母亲教育程度(OR=3.386,95%CI:1.279~8.961)、家庭年收入(OR=8.699,95%CI:2.177~34.765)、患慢性病(OR=0.343,95%CI:0.134~0.881)、优生认知得分(OR=0.906,95%CI:0.836~0.981)、血清HCY水平(OR=1.734,95%CI:1.458~1.986)、异常生育史(OR=3.710,95%CI:1.217~11.308)等因素与子代CHD相关。结论 母亲MTHFR 677C/T多态性与子代CHD发生未发现关联;母亲教育程度低、家庭年收入低、异常生育史、优生认知得分低、血清HCY水平高可能增加子代CHD的发生危险。     

微小RNA前体区域基因多态与肝细胞肝癌遗传易感性关联的研究

目的 探讨微小RNA前体(pre-miRNA)区域基因多态与中国人群肝细胞肝癌(hepatocellular carcinoma,HCC)易感性的关系.方法 采用病例-对照研究设计,包括确诊的HCC患者963例、乙型肝炎病毒(hepatitis B virus,HBV)阳性对照829例和HBV阴性对照852名.选取pre-miRNA区域多态位点hsa-mir-146a rs2910164 C→G及hsa-mir-196-a2 rs11614913 T→C为研究位点,应用引物错配限制性分析(primer introduced restriction analysis-PCR,PIRA-PCR)方法进行多态性检测,应用logistic回归计算OR值及95%CI,比较不同基因型与HCC发病风险的关系.结果 rs2910164位点3种基因型CC、CG、GG在病例组分布频率分别为34.5%(319/925)、48.6%(450/925)、16.9%(156/925),在HBV阳性对照组中分别为36.4%(274/753)、45.0%(339/753)、18.6%(140/753),在HBV阴性对照组中分别为36.1%(303/840)、46.0%(386/840)、18.0%(151/840).rs11614913位点3种基因型TT、CT、CC在病例组分布频率分别为29.7%(277/934)、48.1%(449/934)、22.3%(208/934),在HBV阳性对照组中分别为30.3%(238/785)、51.0%(400/785)、18.7%(147/785),在HBV阴性对照组中分别为28.6%(239/837)、49.8%(417/837)、21.6%(181/837).在调整年龄、性别、吸烟、饮酒因素后,未能发现两位点多态与HCC发病危险之间存在明显关联[与HBV阳性对照相比:hsa-mir-146a rs2910164(GC+GG对CC):校正0R=1.10,95%CI:0.90～1.36;hsa-mir-196-a2 rs11614913(CC+CT对TT):校正OR=1.01,95%CI:0.81～1. 25;与HBV阴性对照相比:hsa-mir-146a rs2910164(GC+GG对CC):校正OR=1.06,95%CI:0.87～1.29;hsa-mir-196-a2 rs11614913(CC+CT对TT):校正OR=0.94,95%CI:0.76～1.16].分别以年龄、性别、吸烟、饮酒进行分层分析也未能发现两多态位点与HCC发病风险相关联.结论 hsa-mir-146a rs2910164 C→G及hsa-mir-196-a2 rs11614913 T→C多态性可能不是中国人群HCC的易感性标志物.

Abstract：

Objective To investigate the relationship between genetic polymorphism in microRNAs (miRNAs) precursor and genetic prediposition of hepatocellular carcinoma (HCC) in Chinese population. Methods A case-control study including 963 HCC cases and 829 HBsAg positive controls and 852 HBsAg negative controls was conducted. hsa-mir-146a rs2910164 C→G and hsa-mir-196-a2 rs11614913 T→C were selected,where the genotypes were determined by the primer introduced restriction analysis-PCR (PIRA-PCR) assay. Odd ratios (ORs) and 95% confidence intervals (CIs) were evaluated by logistic regression analysis to investigate the relationship between onset risk of HCC and different genotypes. Results The genotype frequencies of CC, CG and GG at rs2910164 gene locus were separately 34. 5 % ( 319/925 ) ,48.6% (450/925) and 16.9% ( 156/925 ) in cases; 36.4% ( 274/753 ) ,45.0% ( 339/753 ) and 18. 6%(140/753) in HBsAg positive controls; and 36. 1% (303/840) ,46.0% (386/840) and 18.0% (151/840) in HBsAg negative controls. The genotype frequencies of TT, CT and CC at rs11614913 were respectively 29.7% (277/934) ,48. 1% (449/934) and 22.3% (208/934) in cases; 30. 3% (238/785) ,51.0% (400/785) and 18. 7% (147/785) in HBsAg positive controls; and 28. 6% (239/837) ,49. 8% (417/837) and 21.6% ( 181/837 ) in HBsAg negative controls. No significant relationships were observed between these two single nucleotide polymorphisms (SNPs) and onset risk of HCC after adjusting the factors as age,gender,smoking and drinking status in comparison with HBsAg positive controls: hsa-mir-146a rs2910164 (CG +GG vs CC): adjusting OR = 1.10,95% CI: 0. 90 - 1.36; hsa-mir-196-a2 rs11614913 ( CC + CT vs TT):adjusting OR= 1.01,95% CI: 0. 81 -1.25; as well as in comparison with HBsAg negative controls: hsa-mir-146a rs2910164 ( CG + GG vs CC ): adjusting OR = 1. 06,95% CI: 0. 87 - 1.29; hsa-mir-196-a2 rs11614913 ( CC + CT vs TT ): adjusting OR = 0. 94,95% CI: 0. 76 - 1.16. As well, no significant relationships were observed between these two SNPs and onset risk of HCC in the subgroups stratified by age,gender,smoking and drinking status. Conclusion hsa-mir-146a rs2910164 C→G and hsa-mir-196-a2 rs11614913 T→C may not play an important role in the HCC predisposition among Chinese populations.     

白细胞介素-6基因多态性与尘肺的相关性

目的 研究白细胞介素-6（IL-6）（-634C/G）基因多态性与尘肺的关系.方法 选择确诊的104例Ⅰ期男性矽肺患者66例（矽肺组）、煤工尘肺患者38例（煤工尘肺组）为研究对象,以接触同性质粉尘、非尘肺的122名男性接触矽尘工人77例（矽尘组）、接触煤尘工人45例（煤尘组）为对照;采集外周静脉血,应用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）技术检测IL-6（-634C/G）基因多态性.结果 IL-6（-634C/G）基因型（CC、CG、GG）在矽肺组、矽尘组、煤工尘肺组和煤尘组分布频率分别为66.7%、19.7%、13.6%,42.9%、42.9%、14.2%,73.7%、18.4%、7.9%和51.1%、35.6%、13.3%.成组分析和1：1配对分析中均发现IL-6（-634C/G）基因型分布频率在矽肺组和矽尘组间差异有统计学意义（P＜0.05）.结论 IL-6（-634 C/G）基因多态性与矽肺发病相关.     

5,10-Methylenetetrahydrofolate reductase polymorphisms and pharmacogenetics: a new role of single nucleotide polymorphisms in the folate metabolic pathway in human health and disease

Knowledge about the role of folate, a water-soluble B vitamin, and single nucleotide polymorphisms (SNPs) in the folate metabolic pathway in human health and disease has been rapidly expanding. Recently, functionally significant SNPs in 5,10-methylenetetrahydrofolate reductase (MTHFR), a critical enzyme for intracellular folate homeostasis and metabolism, have been identified and characterized. An emerging body of in vitro and clinical evidence suggests that these MTHFR SNPs may be an important pharmacogenetic determinant of predicting response to and toxicity of methotrexate and 5-fluorouracil-based cancer and anti-inflammatory treatments because of their well-defined and highly relevant biochemical effects on intracellular folate composition and one-carbon transfer reactions.     

孕中期妇女体力活动与血糖代谢的关联性

目的  探究孕中期体力活动与血糖水平及妊娠期糖尿病(gestational diabetes mellitus, GDM)的关联。 方法  采用横断面调查的方法, 于2017-2018年在广州市纳入孕周在20~28周的孕妇1 083人。采用面对面调查收集一般人口学和生活方式等资料, 采用国际体力活动问卷调查过去一周的体力活动, 通过口服葡萄糖耐量试验(oral glucose tolerance test, OGTT)测量孕妇血糖和诊断GDM。运用多重线性回归和Logistic回归分析模型分别探讨不同类型体力活动和静坐行为与血糖及GDM的关联。 结果  36.57%的孕妇体力活动达到推荐值(中高体力活动≥150 min/week)。多重线性回归结果表明, 孕中期妇女总体力活动强度与OGTT-2 h血糖水平呈负相关关系(β=-0.10, P=0.017);运动锻炼和休闲体力活动强度与OGTT-1 h血糖呈负相关(β=-0.11, P=0.042), 未发现其他类型体力活动或静坐时间与血糖之间的关联。Logistic回归分析模型分析未发现各类型体力活动或静坐时间与GDM风险之间的关联。 结论  孕中期妇女体力活动水平较低, 近2/3妇女未达到推荐值。孕中期妇女总体力活动、运动锻炼和休闲体力活动有助于降低餐后血糖。     

Folate intake, serum folate, serum total homocysteine levels and methylenetetrahydrofolate reductase C677T polymorphism in young Japanese women

Various factors influence folate status and requirements. To investigate the folate status in young Japanese women (n=340, 20-22 y), I determined the serum folate and total homocysteine (tHcy), and examined the influence of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism on folate status in a subgroup of 252 of the women. I calculated folate consumption based on records of food intake weighed over 3 d using the standard Tables of Food Composition in Japan (5th revised edition) and the US Food Composition Table based on the USDA nutrient database excluding fortification. Serum folate and total homocysteine (tHcy) levels were determined by chemiluminescent-competitive protein binding assay and HPLC, respectively. The mean intake of folate was 323+/-133 and 196+/-71 microg/d, and 86.5% and 42.1% of the participants consumed more than the RDA of 200 microg of folate, according to the Japanese and US tables, respectively. The main sources of dietary folate were vegetables, green tea and bread. Serum folate levels were significantly correlated with folate intake (r=0.249, p<0.001). Serum tHcy levels were above 15 micromol/L in four participants. I found significant negative correlations between serum tHcy and folate intake (r=-0.175, p<0.05), and between serum tHcy and serum folate (r=-0.297, p<0.0001). The frequencies of the CC, CT and TT genotypes of the MTHFR gene were 32.9, 51.6 and 15.5%, respectively. Among individuals with the TT genotype, serum folate and tHcy levels were lower and higher, respectively, than in those with the other genotypes, regardless of folate intake above RDA. These data suggest that the current RDA of folate estimated based on foreign data might not be sufficient for Japanese and that this value might require reassessment.     

B-vitamins, homocysteine and gene polymorphism in adults with fasting or post-methionine loading hyperhomocysteinemia

Background  Although fasting and post-methionine loading (PML) homocysteine concentrations are not necessarily related, a high percentage of hyperhomocysteinemia cases would be missed if methionine loading was not performed. Aim of the study  The influences of B-vitamins and genetic polymorphism (methylenetetrahydrofolate reductase 677C → T, MTHFR 677C → T) on fasting and PML homocysteine concentrations and the relationship between fasting and PML homocysteine were studied. Methods  This study was a cross-sectional study. Healthy subjects were divided into either fasting hyper-homocysteinemia (≥12.2 μmol/l) (fasting hyper-hcy, n = 51), PML hyper-homocysteinemia (fasting homocysteine <12.2 μmol/l but PML homocysteine ≥25.6 μmol/l) (PML hyper-hcy, n = 29), or normo-homocysteinemia (fasting homocysteine <12.2 μmol/l and PML homocysteine <25.6 μmol/l) (normo-hcy, n = 118) group based on elevated fasting and PML homocysteine levels of the 75th percentile of the population. The concentrations of plasma fasting and PML homocysteine, serum folate, vitamin B-12, plasma pyridoxal 5′- phosphate (PLP) were measured. The genetic polymorphisms were determined. Results  Fasting homocysteine, but not PML homocysteine and MTHFR 677C → T genotype, was significantly and inversely affected by serum folate concentration after adjusting for potential confounders (β = −0.062, P < 0.01). Fasting and PML homocysteine were highly associated in the fasting hyper-hcy and pooled groups (P < 0.01) but not in the PML hyper-hcy and normo-hcy groups. PML homocysteine did not interact with either serum folate (P = 0.302), vitamin B-12 (P = 0.465), plasma PLP (P = 0.996) or MTHFR 677C → T genotype (P = 0.136) to affect fasting homocysteine concentration. Conclusions  Approximately one-third (36.3%) of hyperhomocysteinemia cases would be missed if methionine loading were not performed. Even though subjects may have a normal fasting homocysteine concentration, they need further screening for their PML homocysteine.     

血清同型半胱氨酸、叶酸浓度水平与老年阿尔茨海默病发病的相关性研究

目的研究血清同型半胱氨酸(Hcy)、叶酸浓度水平与老年阿尔茨海默病(AD)发病的相关性,以期为临床防治提供指导。方法将2016年5月-2018年10月于本院接受诊治的92例老年阿尔茨海默病患者作为研究组,另选择同期于本院健康体检者80例为对照组。选择高效液相法对2组人员的血清Hcy表达水平进行测定,并应用化学发光法对血清叶酸水平进行检测;分析血清Hcy、叶酸与AD患者认知功能、生活质量的相关性。结果研究组患者的血清Hcy水平高于对照组,但血清叶酸水平、MMSE评分均低于对照组,差异有统计学意义(P<0.05);研究组患者的血清Hcy过高表达检出率、叶酸过低表达检出率均高于对照组,差异有统计学意义(P<0.05);AD过高Hcy组患者的血清叶酸水平显著低于AD正常Hcy组,差异有统计学意义(P<0.05);经Spearman相关性分析发现,血清叶酸和认知功能、生活质量显示为正相关(r=0.328、r=0.339,P<0.05),而血清Hcy和认知功能、生活质量显示为负相关(r=-0.517、r=-0.502,P<0.05)。结论血清同型半胱氨酸过高表达和老年阿尔茨海默病发病存在直接相关性,即高Hcy血症可能是引发AD的独立危险因素;而人体缺乏叶酸能导致血清Hcy表达升高,故认为叶酸的缺乏可能是引发AD的间接危险因素。     

MAP2K5基因rs2241423多态性与儿童肥胖干预效果的关系

目的 探索MAP2K5基因rs2241423多态性与儿童肥胖干预效果的关系,为未来开展基于遗传背景的个性化干预提供科学依据。方法 在一项研究儿童肥胖干预效果的整群随机对照试验中,选取北京地区382名8~10岁儿童作为研究对象,收集唾液,检测MAP2K5基因rs2241423多态性,并分析基因与干预对儿童肥胖的交互作用。结果 MAP2K5基因rs2241423多态性与干预措施对儿童BMI、BMI Z评分、腰臀比和体重等肥胖相关指标的改变存在交互作用(P_交互分别为0.034、0.007、0.039和0.036)。与对照组相比,干预组儿童在MAP2K5基因rs2241423位点上每多携带一个 G等位基因,BMI下降(-0.36 kg/m²,95%CI:-0.69~-0.03 kg/m²,P=0.034),BMI Z评分降低(-0.20,95%CI:-0.35~-0.06,P=0.007),腰臀比降低(-0.01,95%CI:-0.02~-0.001,P=0.039),体重减少(-0.84 kg, 95%CI:-1.63~-0.06 kg,P=0.036)。结论 在MAP2K5基因rs2241423位点上携带G等位基因的儿童对干预更加敏感,接受干预后可在BMI及 Z评分、腰臀比和体重指标上获得更多改善。