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methylenetetrahydrofolate reductase C677T polymorphism predicts response and time to progression to gemcitabine-based chemotherapy for advanced non-small cell lung cancer in a Chinese Han population

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Journal of Zhejiang University-Science B(Biomedicine & Biotechnology) 2013年第3期14卷 207-215页

作者： Wei HONG Kai WANG Yi-ping ZHANG Jun-yan KOU Dan HONG Dan SU Wei-min MAO Xin-min YU Fa-jun XIE Xiao-jian WANG Department of Medical Oncology Zhejiang Cancer Hospital Zhejiang Key Laboratory of the Diagnosis and Treatment Technology on Thoracic Oncology Department of Respiratory Medicine the Second Affiliated HospitalSchool of MedicineZhejiang University Department of Medical Oncology Hangzhou Cancer Hospital Institute of Immunology School of MedicineZhejiang University

Objective： The aim of this study was to evaluate the association between the methylenetetrahydrofolate reductase （MTHFR） C677T excision repair cross-complementation group 1 （ERCC1） genetic polymorphisms and the clinical efficacy of gemcitabine-based chemotherapy in advanced non-small cell lung cancer （NSCLC）. Methods： A total of 135 chemonaive patients with unresectable advanced NSCLC were treated with gemcitabine/platinum regi- mens. The polymorphisms of MTHFR C677T, ERCC1 C8092A, and ERCC1 Cl18T were genotyped using the TaqMan methods. Results： The overall response rate was 28.9%. Patients with MTHFR CC genotype had a higher rate of objective response than patients with variant genotype （TT or CT）（41.2% versus 19.1%, P=0.01 ）. Median time to progression （TTP） of patients with MTHFR CC genotype was longer than that of patients with variant genotype （7.6 months versus 5.0 months, P=0.003）. No significant associations were obtained between ERCC1 C118T and C8092A polymorphisms and both response and survival. Conclusions： Our data suggest the value of MTHFR C677T polymorphism as a possible predictive marker of response and TTP in advanced NSCLC patients treated with gemcitabine/platinum.

关键词： Non-small cell lung cancer Single nucleotide polymorphism methylenetetrahydrofolate reductase Gemcitabine Excision repair cross-complementation group 1

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methylenetetrahydrofolate reductase C677T and A1298C polymorphisms and gastric cancer susceptibility

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World Journal of Gastroenterology 2014年第32期20卷 11429-11438页

作者： Lei-Zhou Xia Yi Liu Xiao-Zhou Xu Peng-Cheng Jiang Gui Ma Xue-Feng Bu Yong-Jun Zhang Feng Yu Ke-Sen Xu Hua Li Department of General Surgery Affiliated People’s Hospital Jiangsu University Department of Hepatobiliary Surgery Qilu Hospital Shandong University Department of Surgery Chang-Hai Hospital The Second Military Medical University

AIM: To identify the association between methylenetetrahydrofolate reductase (MTHFR) polymorphisms and gastric cancer (GC) susceptibility.

关键词： methylenetetrahydrofolate reductase Polymorphism Gastric cancer Meta-analysis

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methylenetetrahydrofolate reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients

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Chinese Medical Sciences Journal 2021年第2期36卷 103-109页

作者： Kunrong Wu Shufang Zhang Ziwan Guan Xiaoli Li Rui Li Ying Yin Yan Li Department of Clinical Pharmacy The First Affiliated Hospital of Shandong First Medical UniversityJinan 250014China School of Pharmaceutical Sciences Shandong First Medical University(Shandong Academy of Medical Sciences)Tai'an 271000ShandongChina

Objective Chronic cardiovascular diseases induced by long-term poor blood glucose control are the main cause of death in patients with type 2 diabetes mellitus(T2DM).Previous researches report that methylenetetrahydrofolate reductase gene(MTHFR)polymorphisms might influence the occurrence of coronary heart disease(CHD)in T2DM *** purpose of this study was to evaluate whether MTHFR C677T and A1298C mutations are associated with the risk of CHD inT2DM *** A total of 197 subjects with T2DM were studied,of which 95 patients with *** genotypes of MTHFR C677T and A1298C were analyzed by using dideoxy chain-termination method,and compared between patients with CHD and those without *** We found that the frequency of the 677T allele was significantly higher in T2DM patients with CHD than those without CHD(P=0.011).However,there was no significant difference in any of the examined haplotypes between T2DM patients with and without ***,the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine(Hey)levels(≤15μmol/L)(P=0.006),while no effect of MTHFR gene polymorphism on the incidence of CHD was found in patients with higher Hey levels(>15 μmol/L)(P=0.491).Conclusion The MTHFR C677T gene polymorphism is associated with the risk of CHD of diabetic patients and could be used as an effective marker for CHD in Chinese diabetic populations with normal Hey levels.

关键词： methylenetetrahydrofolate reductase gene polymorphism type 2 diabetes mellitus coronary heart diseases homocysteine

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Folate levels in mucosal tissue but not methylenetetrahydrofolate reductase polymorphisms are associated with gastric carcinogenesis

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World Journal of Gastroenterology 2006年第47期12卷 7591-7597页

作者： Yu-Rong Weng Dan-Feng Sun Jing-Yuan Fang wei-Qi Gu Hong-Yin Zhu Shanghai Institute of Digestive Disease ShanghaiJiao-Tong University School of Medicine Renji HospitalShanghai 200001 China

AIM: To evaluate whether folate levels in mucosal tissue and some common methylenetetrahydrofolate reductase (MTHFR) variants are associated with the risk of gastric cancer through DNA methylation. METHODS: Real-time PCR was used to study the expression of tumor related genes in 76 mucosal tissue samples from 38 patients with gastric cancer. Samples from the gastroscopic biopsy tissues of 34 patients with chronic superficial gastritis (CSG) were used as controls. Folate concentrations in these tissues were detected by the FOL ACS: 180 automated chemiluminescence system. MTHFR polymorphisms were analyzed by PCR-RFLP, and the promoter methylation of tumor-related genes was determined by methylation-specific PCR (MSP). RESULTS: Folate concentrations were significantly higher in CSG than in cancerous tissues. Decreased expression and methylation of c-myc accompanied higher folate concentrations. Promoter hypermethylation and loss of p16INK4A in samples with MTHFR 677CC were more frequent than in samples with the 677TT or 677CT genotype. And the promoter hypermethylation and loss of p21WAF1 in samples with MTHFR 677CT were more frequent than when 677CC or 677TT was present. The 677CT genotype showed a non-significant higher risk for gastric cancer as compared with the 677CC genotype. CONCLUSION: Lower folate levels in gastric mucosal tissue may confer a higher risk of gastric carcinogenesisthrough hypomethylation and overexpression of c-myc.

关键词： Folate methylenetetrahydrofolate reductase Polymorphism DNA methylation Gastric cancer

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Is the C677T polymorphism in methylenetetrahydrofolate reductase gene or plasma homocysteine a risk factor for diabetic peripheral neuropathy in Chinese individuals?

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Neural Regeneration Research 2012年第30期7卷 2384-2391页

作者： Hongli Wang Dongsheng Fan Tianpei Hong Department of Neurology Peking University Third Hospital Beijing 1 O0191 China

The present study enrolled 251 diabetic patients, including 101 with neuropathy and 150 without neuropathy. Of the 150 patients, 100 had no complications, such as retinopathy, nephropathy, or neuropathy. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to identify methylenetetrahydrofolate reductase gene variants. Plasma homocysteine levels were also measured. Homocysteine levels and the frequency of hyperhomocysteinemia were significantly higher in patients with diabetic peripheral neuropathy compared with diabetic patients without neuropathy （P 〈 0.05）. In logistic regression analysis with neuropathy as the dependent variable, the frequency of C677T in methylenetetrahydrofolate reductase was significantly higher in patients with diabetic peripheral neuropathy compared with patients without diabetic complications. Homocysteine levels were significantly higher in patients with diabetic peripheral neuropathy carrying the 677T allele and low folic acid levels. In conclusion, hyperhomocysteinemia is an independent risk factor for diabetic neuropathy in Chinese patients with diabetes. The C677T polymorphism in methylenetetrahydrofolate reductase and low folic acid levels may be risk factors for diabetic peripheral neuropathy in Chinese patients with diabetes.

关键词： homocysteine methylenetetrahydrofolate reductase type 2 diabetes mellitus diabetic peripheralneuropathy neural regeneration

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Polymorphism of methylenetetrahydrofolate reductase gene is associated with response to fluorouracil-based chemotherapy in Chinese patients with gastric cancer

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Chinese Medical Journal 2014年第20期127卷 3562-3567页

作者： Zhang Xiaoping Bai Zhibin Chen Baoan Feng Jifeng Yan Feng Jiang Zhi Zhong Yuejiao Wu Jianzhong Cheng Lu Lu Zuhong Tong Na Zhang Zhengdong Department of Hematology and OncologyZhongda Hospital Medical School Southeast University NanjingJiangsu 210009 China Department of Invasive Technology &Vascular Surgery Zhongda Hospital Medical School Southeast University NanjingJiangsu 210009 China Department of Oncology Medical School Southeast UniversityNanjing Jiangsu 210009 China Jiangsu Province Cancer Institute Nanjing Jiangsu 210009 China National Key Laboratory for Bioelectronics School of BiologicalScience and Medical Engineering Southeast University NanjingJiangsu 210096 China Department ot Epidemiology and Biostatistics Nanjing MedicalUniversity Nanjing Jiangsu 210029 China

Background The importance of polymorphisms in the methylenetetrahydrofolate reductase （MTHFR） gene for the prediction of the response to fluorouracil-based adjuvant chemotherapy in gastric cancer patients remains unclear. The aim of this study is to assess the predictive value of several polymorphisms of the MTHFR gene for clinical outcomes of gastric cancer patients treated with fluorouracil-based adjuvant chemotherapy in Chinese population. Methods Three hundred and sixty-two Chinese patients with gastric cancer were treated with fluorouracil-based adjuvant chemotherapy. DNA samples were isolated from peripheral blood collected before treatment. The three single nucleotide polymorphisms （SNPs）（rs1801131, rs1801133, rs2274976） genotypes of the MTHFR gene were determined by matrix- assisted laser desorption/ionization time-of-flight mass spectrometry （MALDI-TOF MS）. Results The average response rate for chemotherapy was 46.7%. Homozygous genotypes rs2274976G/G （X2=22.7, P 〈0.01） and rs1801131A/A （X2=14.3, P=0.008） were over-represented in responsive patients. Carriers of the rs2274976A allele genotypes （G/A and A/A） and of the rs1801131C allele genotypes （A/C and C/C）were prevalent in nonresponsive patients. In the haplotype association analysis, there was a significant difference in global haplotype distribution between the groups （X2=20.69, P=0.000 124）. Conclusions These results suggest that polymorphisms of the MTHFR gene may be used as predictors of the response to fluorouracil-based chemotherapy for gastric cancer patients in Chinese population. Well-designed, comprehensive, and prospective studies on determining these polymorphisms of MTHFR gene as clinical markers for predicting the response to fluorouracil-based therapy in gastric cancer patients is warranted.

关键词： gastric cancer single nucleotide polymorphisms methylenetetrahydrofolate reductase fluorouracil

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The methylenetetrahydrofolate reductase genotype 677CT and non-alcoholic fatty liver disease have a synergistic effect on the increasing homocysteine levels in subjects from Chongqing,China

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Genes & Diseases 2019年第1期6卷 88-95页

作者： Xiaolin Wang Yongli Zhou Mingjun Zhang Yonghong Wang Bo Qin Health Management Center The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Neurology The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina Department of Infectious Diseases The First Affiliated Hospital of Chongqing Medical UniversityChongqingChina

The methylenetetrahydrofolate reductase(MTHFR)genotypes 677CT and 677TT are associated with elevated serum homocysteine(Hcy)levels by means of lowering the activity of MTHFR,and the increase in serum Hcy may be linked to increased susceptibility to nonalcoholic fatty liver disease(NAFLD).However,there are contradictory reports of the relationship among the MTHFR 677CT gene polymorphism,Hcy,and ***,the aim of this study was to identify potential associations and interactions of either Hcy levels or the MTHFR 677CT gene polymorphism with the susceptibility to NAFLD in a Chinese *** association between the MTHFR 677 CT gene polymorphism and Hcy levels was determined in 243 subjects with NAFLD and 388 healthy subjects without NAFLD using polymerase chain reactionrestriction fragment length polymorphism analysis and high-performance liquid *** subjects with NAFLD,there was no statistical difference in the genotypic and allelic frequencies of the MTHFR 677 CT gene polymorphism,while serum Hcy levels were significantly higher in subjects with ***,these results strongly suggest that the MTHFR 677CT gene polymorphism and NAFLD have a potential synergistic effect on Hcy elevation,although the MTHFR 677CT gene polymorphism was not correlated with NAFLD in a Chinese population.

关键词： Gene polymorphism Homocysteine methylenetetrahydrofolate reductase Nonalcoholic fatty liver disease Synergistic effect

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Lemierre's syndrome with double heterozygote status in the methylenetetrahydrofolate reductase gene

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World Journal of Pediatrics 2014年第3期10卷 281-283页

作者： Mostafa Behpour-Oskooee Abdollah Karimi Shirin Sayyahfar Pediatric Infectious Diseases Department of PediatricsNajmieh HospitalBaghyatollah University of Medical SciencesTehranIran Pediatric Infectious Diseases Pediatric Infectious Research CenterMofi d Children HospitalShahid Beheshti University of Medical SciencesTehranIran Pediatric Infectious Diseases Department of PediatricsAli Asghar Children HospitalIran University of Medical SciencesTehranIran

Background:There are some risk factors being more vulnerable to Lemierre's syndrome such as a hypercoagulable ***:We report a rare case of Lemierre's syndrome with ethmoid and maxillary sinusitis,bilateral mastoiditis,and sigmoid sinus ***:Genetic study revealed a double heterozygote status in the methylenetetrahydrofolate reductase gene including C677T and ***:It is suggested to screen patients with Lemierre's syndrome for a hypercoagulable state to consider anticoagulant therapy.

关键词： Lemierre's syndrome mastoiditis methylenetetrahydrofolate reductase sigmoid sinus thrombosis

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methylenetetrahydrofolate reductase(MTHFR) polymorphism susceptibility to schizophrenia and bipolar disorder:an updated meta-analysis

Methylenetetrahydrofolate reductase(MTHFR) polymorphism susc...

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2015年度安徽省流行病与卫生统计学学术论坛

作者： Cai-Yun Hu Zhen-Zhong Qian Feng-Feng Gong Shan-Shan Lu Fang Feng Yi-Le Wu Hui-Yun Yang Ye-Huan Sun Department of Epidemiology and Health Statistics School of Public HealthAnhui Medical University Centre for Evidence-Based Practice Anhui Medical University

Previous studies examining the possible role of the methylenetetrahydrofolate reductase(MTHFR) polymorphisms in the development of schizophrenia(SZ) and bipolar disorder(BPD) have provided inconclusive findings,this meta-analysis was therefore designed to get a more reliable assessment.A total of 38 articles were identified through a search of electronic databases,up to 27 February *** ratios(ORs) with 95 % confidence interval(CIs) were calculated using random effects ***-analysis showed that MTHFR C677 T was significantly associated with SZ,the highest OR was found for the recessive model(for TT ***+CC:OR = 1.34,95 % CI:1.18–1.53);a marginal association of MTHFR C677 T with increased risk of BPD has also been found for the recessive model(OR = 1.26,95 % CI:1.00–1.59).Subgroup analysis by ethnicity indicated that the significant association with SZ and BPD existed among Asian and African populations,but not for the *** A1298 C was significant associated with SZ,the highest OR for the dominant model(OR = 1.13,95 % CI:1.03–1.24).Subgroup analysis indicated a significant association with SZ existed in Asian populations,not among the white populations and no significant association was detectedbetween the MTHFR A1298 C and BPD in all *** conclude that MTHFR polymorphism is associated with SZ and BPD among Asian,African populations,but not the white.

关键词： methylenetetrahydrofolate reductase MTHFR Polymorphism Schizophrenia Bipolar disorder Meta-analysis

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Effects of methylenetetrahydrofolate reductase single-nucleotide polymorphisms on breast,cervical,ovarian,and endometrial cancer susceptibilities

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Chronic Diseases and Translational Medicine 2021年第3期7卷 169-181页

作者： Wang Zheng Kai Li Ling Ouyang Hidasa Iko Ahmad Javid Safi Shan Gao Department of Otorhinolaryngology The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110001China Department of Surgical Oncology The First Affiliated Hospital of China Medical UniversityShenyangLiaoning 110001China Department of Obstetrics and Gynecology The Shengjing Hospital of China Medical UniversityShenyangLiaoning 110001China Japan Shouko Co.Ltd Nisikujo 3-5-4 Konohanaku Osakashi Osakafu Japan554-0012Japan Afghanistan Cancer Foundation Kart-e-CharKabulAfghanistan

Background:Recent studies identifying methylenetetrahydrofolate reductase(MTHFR)polymorphisms associated with breast cancer(BC),ovarian cancer(OC),cervical cancer,and endometrial cancer(EC)have reported conflicting results and been *** clarify the correlation betweenMTHFR mutations and these common female malignancies,we conducted a comprehensive meta-analysis incorporating all eligible ***:Relevant reports published before January 20,2020,were retrieved from PubMed,Embase,the Cochrane Library,and the China National Knowledge Infrastructure *** odds ratio and 95% confidence interval summaries for theMTHFR 677C/T and 1298A/C polymorphisms in BC,OC,cervical cancer,and EC were ***:A total of 171 studies comprising 56,675 cancer cases and 67,559 controls were *** results showed a markedly elevated risk of cancer susceptibility related toMTHFR 677C/T based on all genetic ***,we identified a significant correlation between 1298A/C mutation and cancer risk based on overall comparisons among all models,except the heterozygous ***,subgroup analysis by cancer type revealed a significantly increased risk of BC associated with 677C/T in the five models and of cervical cancer associated with 1298A/C in some *** on ethnicity,significant associations were observed between Asian,African,and mixed populations for 677C/T and the Asian population for 1298A/*** regard to the sample type used for analysis,we detected a positive association between using blood as the DNA source and cancer risk for 677C/T in all genetic models and for 1298A/C in some genetic *** stratification of the results revealed that a notably increased risk was associated with the use of polymerase chain reaction-restriction fragment-length polymorphism or TaqMan as the genotyping method,as well as with the use of population-or hospital-based groups as the controls for 677C/T and 1298A/C,***

关键词： methylenetetrahydrofolate reductase Breast cancer Female genital neoplasms Polymorphism Meta-analysis

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