[1]任炳楠),王连珂),田丹丹),等.BHMT rs3733890基因多态性与叶酸治疗河南汉族HHcy患者效果的前瞻性队列研究[J].郑州大学学报(医学版),2019,(06):815-819.[doi:10.13705/j.issn.1671-6825.2019.01.003]
 REN Bingnan),WANG Lianke),TIAN Dandan),et al.BHMT gene rs3733890 polymorphism and the efficacy of oral folate therapy for Henan Han population with hyperhomocysteinemia:a prospective cohort study[J].JOURNAL OF ZHENGZHOU UNIVERSITY(MEDICAL SCIENCES),2019,(06):815-819.[doi:10.13705/j.issn.1671-6825.2019.01.003]
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BHMT rs3733890基因多态性与叶酸治疗河南汉族HHcy患者效果的前瞻性队列研究()
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《郑州大学学报(医学版)》[ISSN:1671-6825/CN:41-1340/R]

卷:
期数:
2019年06期
页码:
815-819
栏目:
论著
出版日期:
2019-11-20

文章信息/Info

Title:
BHMT gene rs3733890 polymorphism and the efficacy of oral folate therapy for Henan Han population with hyperhomocysteinemia:a prospective cohort study
作者:
任炳楠1)王连珂1)田丹丹2)王文华1)田惠子1)韩 涵3)岳利敏1)杜冰会1)张卫东1)
1)郑州大学公共卫生学院流行病学教研室 郑州 450001 2)河南省人民医院高血压科 郑州 450003 3)郑州大学公共卫生学院营养与食品卫生学教研室 郑州 450001
Author(s):
REN Bingnan1)WANG Lianke1)TIAN Dandan2)WANG Wenhua1)TIAN Huizi1)HAN Han3)YUE Limin1)DU Binghui1)ZHANG Weidong1)
1)Department of Epidemiology, College of Public Health, Zhengzhou University, Zhengzhou 450001 2)Department of Hypertension, Henan Provincial People's Hospital, Zhengzhou 4500033)Department of Nutrition and Food Hygiene, College of Public Health, Zhengzhou University, Zhengzhou 450001
关键词:
河南汉族人群 甜菜碱同型半胱氨酸甲基转移酶 高同型半胱氨酸血症 基因多态性 叶酸 交互作用
Keywords:
Henan Han population Betaine-homocysteine methyltransferase hyperhomocysteinemia gene polymorphism folate interaction
分类号:
R333.6
DOI:
10.13705/j.issn.1671-6825.2019.01.003
摘要:
目的:探讨甜菜碱同型半胱氨酸甲基转移酶(BHMT)rs3733890基因多态性与叶酸治疗高同型半胱氨酸血症(HHcy)效果的关联,并分析基因-环境交互作用对疗效的影响。方法:使用前瞻性队列研究,收集2014年7月至12月郑州大学第五附属医院收治的1 071例HHcy患者,对其采血并检测血浆同型半胱氨酸(Hcy)水平,随后进行90 d的口服叶酸(5 mg/d)干预治疗。治疗结束时复查血浆Hcy水平,根据复查结果将患者分入治疗成功组(Hcy≤15 μmol/L)和治疗失败组(Hcy>15 μmol/L)。通过MassArray平台对BHMT rs3733890进行基因分型。运用基于logistic回归的分层分析探究基因-环境的交互作用。结果:①rs3733890基因型在两组间的分布差异有统计学意义(P<0.05)。②携带突变基因型(GA+AA)和突变等位基因(A)的患者,叶酸治疗失败的风险明显升高(P<0.05)。③突变基因型与不良生活习惯(吸烟、饮酒)和既往史(糖尿病、高血压、冠心病)分别存在交互作用。结论:BHMT rs3733890基因多态性与叶酸干预治疗河南汉族HHcy的疗效存在关联,该位点与环境因素的交互作用会影响叶酸治疗效果。
Abstract:
Aim:To investigate the association between BHMT gene rs3733890 polymorphism and the efficacy of oral folate therapy for patients with hyperhomocysteinemia(HHcy)and analyze the effects of gene-environment interactions on the efficacy of therapy.Methods:We utilized a prospective cohort study among the Chinese Han population. All HHcy participants were outpatients treated at the Fifth Affiliated Hospital of Zhengzhou University from July to December 2014. Blood samples were collected from 1 071 eligible patients at baseline, and these individuals received folate treatment(5 mg/d)for 90 days. A total of 638 patients included in the final analysis were grouped into the treatment success group[homocysteine(Hcy)≤15 μmol/L] and the treatment failure group(Hcy>15 μmol/L)based on post-treatment Hcy levels. Time-of-flight mass spectrometry(MassArray system)was used to assess the genotype of BHMT rs3733890. The stratified analysis was used to explore potential gene-environmental interactions based on logistic regression.Results:The genotype distribution presented distinct differences between the two groups(P<0.05). The patients with mutant genotype(GA+AA)and allele(A)had increased risk of treatment failure(P<0.05). Furthermore, synergistic effects of BHMT rs3733890 polymorphism with smoking, drinking as well as previous history on the efficacy of oral folate therapy were also found.Conclusion:The polymorphism of BHMT rs3733890 is strongly associated with the efficacy of oral folate therapy in Henan Han population with HHcy. The combinations of genetic mutations of BHMT rs3733890 and undesirable environmental factors could directly influence the efficacy of folate treatment for HHcy.

参考文献/References:

[1] HUANG T,YUAN GF,ZHANG ZG,et al.Cardiovascular pathogenesis in hyperhomocysteinemia[J].Asia Pac J Clin Nutr,2008,17(1):8
[2] VAN DER GRIEND R,HAAS FJ,DURAN M,et al.Methionine loading test is necessary for detection of hyperhomocysteinemia[J].J Lab Clin Med,1998,132(1):67
[3] MARON BA,LOSCALZO J.The treatment of hyperhomocysteinemia[J].Annu Rev Med,2009,60:39
[4] CYBULSKA B,KLOSIEWICZ-LATOSZEK L.Homocysteine:is it still an important risk factor for cardiovascular disease?[J].Kardiol Pol,2015,73(11):1092
[5] GANGULY P,ALAM SF.Role of homocysteine in the development of cardiovascular disease[J].Nutr J,2015,14:6
[6] TIGHE P,WARD M,MCNULTY H,et al.A dose-finding trial of the effect of long-term folic acid intervention:implications for food fortification policy[J].Am J Clin Nutr,2011,93(1):11
[7] THAMBYRAJAH J,LANDRAY MJ,JONES HJ,et al.A randomized double-blind placebo-controlled trial of the effect of homocysteine-lowering therapy with folic acid on endothelial function in patients with coronary artery disease[J].J Am Coll Cardiol,2001,37(7):1858
[8] BROUWER IA,VAN DUSSELDORP M,THOMAS CM,et al.Low-dose folic acid supplementation decreases plasma homocysteine concentrations: a randomized trial[J].Am J Clin Nutr,1999,69(1):99
[9] VAN DER GRIEND R,BIESMA DH,HAAS FJ,et al.The effect of different treatment regimens in reducing fasting and postmethionine-load homocysteine concentrations[J].J Intern Med,2000,248(3):223
[10]JI C,SHINOHARA M,KUHLENKAMP J,et al.Mechanisms of protection by the betaine-homocysteine methyltransferase/betaine system in HepG2 cells and primary mouse hepatocytes[J].Hepatology,2007,46(5):1586
[11]DA SL,GALBIATTI AL,RUIZ MT,et al.MTHFD1 G1958A,BHMT G742A,TC2 C776G and TC2 A67G polymorphisms and head and neck squamous cell carcinoma risk[J].Mol Biol Rep,2012,39(2):887
[12]BOYLES AL,BILLUPS AV,DEAK KL,et al.Neural tube defects and folate pathway genes: family-based association tests of gene-gene and gene-environment interactions[J].Environ Health Perspect,2006,114(10):1547
[13]XU X,GAMMON MD,ZEISEL SH,et al.High intakes of choline and betaine reduce breast cancer mortality in a population-based study[J].FASEB J,2009,23(11):4022
[14]MOSTOWSKA A,MYKA M,LIANERI M,et al.Folate and choline metabolism gene variants and development of uterine cervical carcinoma[J].Clin Biochem,2011,44(8/9):596
[15]ZAMPIERI BL,BISELLI JM,GOLONI-BERTOLLO EM,et al.BHMT G742A and MTHFD1 G1958A polymorphisms and down syndrome risk in the brazilian population[J].Genet Test Mol Biomarkers,2012,16(6):628
[16]MOSTOWSKA A,HOZYASZ KK,WOJCICKI P,et al.Associations of folate and choline metabolism gene polymorphisms with orofacial clefts[J].J Med Genet,2010,47(12):809
[17]TIAN HZ,TIAN DD,ZHANG CD,et al.Efficacy of folic acid therapy in patients with hyperhomocysteinemia[J].J Am Coll Nutr,2017,36(7):528
[18]FINKELSTEIN JD. The metabolism of homocysteine: pathways and regulation[J]. Eur J Pediatr,1998,157(Suppl 2):S40
[19]DU BH,TIAN HZ,TIAN DD,et al.Genetic polymorphisms of key enzymes in folate metabolism affect the efficacy of folate therapy in patients with hyperhomocysteinaemia[J].Br J Nutr,2018,119(8):887
[20]HEIL SG,LIEVERS KJ,BOERS GH,et al.Betaine-homocysteine methyltransferase(BHMT): genomic sequencing and relevance to hyperhomocysteinemia and vascular disease in humans[J].Mol Genet Metab,2000,71(3):511
[21]LI F,FENG Q,LEE C,et al.Human betaine-homocysteine methyltransferase(BHMT)and BHMT2:common gene sequence variation and functional characterization[J].Mol Genet Metab,2008,94(3):326
[22]LIU Y,LIU YQ,MORITA T,et al.Effect of dietary supplementation with folate on choline deficiency-induced hyperhomocysteinemia in rats[J].J Nutr Sci Vitaminol(Tokyo),2012,58(1):20
[23]HOBBS CA,CLEVES MA,KARIM MA,et al.Maternal Folate-Related Gene Environment Interactions and Congenital Heart Defects[J].Obstet Gynecol,2010,116(2, 1):316
[24]ONO H,IWASAKI M,KUCHIBA A,et al.Association of dietary and genetic factors related to one-carbon metabolism with global methylation level of leukocyte DNA[J].Cancer Sci,2012,103(12):2159

备注/Memo

备注/Memo:
【基金项目】河南省科技发展计划项目(132102310431) 【作者简介】张卫东,通信作者,男,1963年10月生,博士,教授,研究方向:感染性疾病与分子流行病学、临床流行病学,E-mail:imooni@163.com
更新日期/Last Update: 2019-11-20