DPD、MTHFR和TS表达水平与氟尿嘧啶类药物治疗消化道肿瘤疗效及预后关系的研究进展

消化道恶性肿瘤包括结直肠癌、胃癌和食管癌等。尽管使用了各种治疗方式，癌症患者仍然有复发和转移。绝大多数患者确诊时即为中晚期，因而化疗在癌症患者中发挥重要作用。作为5-FU抗癌活性中的三个关键酶，二氢嘧啶脱氢酶（DPD）、5,10-亚甲基四氢叶酸还原酶（MTHFR）、胸苷酸合成酶（TS）与消化道肿瘤的疗效、对化疗药物的敏感性及患者的预后有密切关系。     

Methylenetetrahydrofolate reductase A1298C polymorphism and diabetes risk: evidence from a meta-analysis

Aim: The relationship between the methylenetetrahydrofolate reductase (MTHFR) A1298C polymorphism and the susceptibility of diabetes remains inclusive or controversial. For better understanding of the influence of MTHFR A1298C polymorphism on diabetes risk, we performed this meta-analysis. Methods: All related articles were identified through a search of PubMed, Embase, Chinese Biomedical Literature Database (CBM, Chinese), China National Knowledge Infrastructure (CNKI), and Wangfang Database (Chinese). The relationship between the MTHFR A1298C polymorphism and diabetes susceptibility was conducted by odds ratios (ORs) and 95% confidence intervals. Results: Total of six studies with 897 cases and 852 controls were included in our meta-analysis. Overall, the significance associated was found between MTHFR A1298C polymorphism and the susceptibility of diabetes under recessive model (CC vs. AC/AA: OR?=?1.70, 95% CI?=?1.18–2.45, p?=?0.004). On the subgroup analysis according to ethnicity, the results indicated that MTHFR A1298C polymorphism has a significant association with diabetes in Asian population under dominant model (CC/AC vs. AA: OR?=?1.31, 95% CI?=?1.003–1.72, p?=?0.047). However, there was no association found between MTHFR A1298C polymorphism and diabetes susceptibility in Caucasians. Conclusions: The results indicated that the MTHFR A1298C polymorphism is a dangerous factor for diabetes, especially for Asians.     

中国汉族人群NR3C1 MTHFR和IGFBP3基因多态性及DNA甲基化与激素性股骨头坏死风险的相关分析

目的 探究NR3C1、MTHFR和IGFBP3基因多态性及DNA甲基化状态与激素性股骨头坏死(SONFH)之间的关系。方法 本病例对照研究中,选自合肥及周边地区包括79例短期冲击或长期口服糖皮质激素治疗SONFH的患者为病例组,114例服用糖皮质激素但未发生SONFH的患者为对照组。评估两组NR3C1、MTHFR和IGFBP3基因中的5个单核苷酸多态性(SNPs),这些SNPs由iMLDR进行基因分型。采用MethylTarget技术检测阳性位点(CpG位点)的甲基化水平,利用e QTLD技术分析以上3个基因的SNPs与甲基化水平的相互作用。结果 病例组与对照组相比,rs3110697 A/G基因型携带者患病风险低;在隐性遗传模型下,rs3110697 A等位基因携带者患病风险低;CpG位点IGFBP3_ 2-143、MTHFR_1-36、MTHFR_1-77、MTHFR_1-139、MTHFR_2-42、NR3C1_2-163、NR3C1_4-47甲基化水平差异显著,差异有统计学意义(P<0.05);共有10对SNPs与甲基化位点线性回归检验差异有统计学意义(P<0.05)。结论 SONFH是一种多基因病,其3个关联基因NR3C1、MTHFR和IGFBP3中的SNPs与DNA甲基化水平均存在广泛交互作用,有助于进一步建立SONFH基因调控模型指导临床诊疗。     

湖北省英山县汉族女性MTHFR和MTRR的遗传多态性分析

目的分析湖北省黄冈市英山县汉族育龄女性叶酸代谢相关酶5,10-亚甲基四氢叶酸还原酶(MTHFR)和甲硫氨酸合成酶还原酶(MTRR)的基因多态性分布特征,以指导育龄女性增补叶酸和出生缺陷的一级预防。方法以英山县319例汉族女性为研究对象,提取口腔黏膜上皮细胞基因组DNA,通过荧光定量PCR法对MTHFR和MTRR的多态性位点进行分析,获得英山县妇女该基因的分布特征,并与已报道的其他地区的数据进行比较。结果英山县汉族女性MTHFR C677T基因型构成与淄博、济源、张家口、延边、乌鲁木齐、银川、眉山、南宁、琼海数据相比差异有统计学意义(x^2值为181.41~13.46,均P<0.05),与松滋、湘潭、惠州相比无统计学意义(x^2值为0.12~5.87,均P>0.05)。英山县汉族女性MTHFR A1298C基因型构成与淄博、济源、张家口、延边、银川、眉山、松滋、湘潭数据的差异均有统计学意义(x^2值为76.94~7.31,均P<0.05),与乌鲁木齐、惠州、南宁、琼海相比无统计学意义(x^2值为5.19~0.97,均P>0.05)。英山县汉族女性MTRR A66G的基因型构成与延边和琼海的差异有统计学意义(x^2值分别为6.10、17.10,均P<0.05),与淄博、济源、张家口、乌鲁木齐、银川、眉山、松滋、湘潭、惠州、南宁的差异均没有统计学意义(x^2值为0.95~5.48,均P>0.05)。结论英山县汉族女性MTHFR和MTRR基因多态性频率分布具有地域特异性。     

Synergistic effect of MTHFR C677T and F2 G20210A polymorphisms on ischemic stroke

The predisposition to stroke might involve interactive effects among variants in several genes.We tested this hypothesis by examining the influence of polymorphisms in methylenetetrahydrofolate reductase（MTHFR）（C677T） and prothrombin（F2）（G20210A） as risk factors for stroke in Morocco.The polymerase chain reaction-restriction fragment length polymorphism methods were used to analyze DNA from 91 stroke patients and 182 controls.Association between the two polymorphisms and the risk of stroke was estimated by four-level models for the analysis of genetic interaction.Neither the MTHFR 677TT nor the F2 20210GA genotype showed any significant association compared to the MTHFR CC and F2 GG genotypes,respectively.An interactive effect between the MTHFR 677TT and F2 20210GA polymorphisms showed an increased risk of stroke.The odds ratios,in univariate and multivariate analysis,for the combined polymorphisms were 4.99（95% CI,1.75–14.2,P = 0.001） and 5.29（95% CI,1.63–17.1,P = 0.005）,respectively.     

Serum total homocysteine,folate, 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T genotype and subclinical atherosclerosis

Objective: To determine the relationship of serum total homocysteine (tHcy), serum folate and 5,10-methylenetetrahydrofolate reductase (MTHFR) 677C→T genotype with ultrasonic arterial wall measurements associated with subclinical atherosclerosis. Study design: Cross-sectional analysis of 767 participants in an ongoing prospective study. Intima-media thickness (IMT) of the common carotid (IMTcc), IMT of the internal carotid including plaque when present (IMT_max) and the sum of the thickest plaques present in both carotid and both common femoral bifurcations (total plaque thickness (TPT)) were measured using ultrasound. Results: People in the upper homocysteine quartile were more likely to have clinical cardiovascular disease (CVD) than those in the lowest three quartiles. They were also more likely to have plaques. The MTHFR 677C→T genotype was not associated with any of the measures of subclinical atherosclerosis in either men or women but was the most important determinant of total homocysteine levels in men under 60 years of age. Conclusions: Increased homocysteine levels but not MTHFR 677C→T genotype, are associated with subclinical atherosclerosis and the presence of plaques. Our results indicate that measurements of blood levels of homocysteine and folate in people at intermediate risk for atherosclerotic CVD before symptoms occur, might improve risk stratification and facilitate the decision to provide folate/B vitamin intervention in primary prevention.     

Association of Methylenetetrahydrofolate Reductase Gene 677C>T Polymorphism with Hypertension in Older Women in a Population of Buenos Aires City

We examined the relationship between the 677C >T polymorphism in the MTHFR gene and tHcy in normotensive (NT) and hypertensive (HT) subjects and the influence of sex and age in a cross-sectional study. Smoking habits, history of vascular disease, diabetes, and tHcy were significantly associated with T allele as hypertension risk factors. The T allele was significantly related with higher tHcy in (i) men versus women (P < .01), (ii) men and women older than 47 years versus the younger ones (P < .05 and P < .001, respectively), (iii) HT women versus NT women (P < .01), and (iv) older HT women versus older NT women (P < .01). We found an association between the 677C>T MTHFR polymorphism and tHcy with hypertension that in women is manifested with age.