
FOLLOWUS
1Department of Clinical Pharmacy, The First Affiliated Hospital of Shandong First Medical University, Jinan 250014, China
2School of Pharmaceutical Sciences, Shandong First Medical University (Shandong Academy of Medical Sciences) Tai’an 271000, Shandong, China
*Tel: 86-13791126823, E-mail: prof_liyan@126.com
收稿日期:2020-08-18,
网络出版日期:2020-12-01,
纸质出版日期:2021-06-30
Scan QR Code
吴坤荣, 张恕芳, 关紫菀, 等. 亚甲基四氢叶酸还原酶基因C677T多态性与中国2型糖尿病患者冠心病风险增加相关[J]. 中国医学科学杂志(英文版), 2021,36(2):103-109.
Wu Kunrong, Zhang Shufang, Guan Ziwan, et al. Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients[J]. Chinese medical sciences journal, 2021, 36(2): 103-109.
吴坤荣, 张恕芳, 关紫菀, 等. 亚甲基四氢叶酸还原酶基因C677T多态性与中国2型糖尿病患者冠心病风险增加相关[J]. 中国医学科学杂志(英文版), 2021,36(2):103-109. DOI: 10.24920/003792.
Wu Kunrong, Zhang Shufang, Guan Ziwan, et al. Methylenetetrahydrofolate Reductase Gene Polymorphism C677T is Associated with Increased Risk of Coronary Heart Disease in Chinese Type 2 Diabetic Patients[J]. Chinese medical sciences journal, 2021, 36(2): 103-109. DOI: 10.24920/003792.
目的
长期血糖控制不佳引起的慢性心血管疾病是2型糖尿病患者主要的死亡原因。研究表明:亚甲基四氢叶酸还原酶基因(methylenetetrahydrofolate reductase gene
MTHFR
)多态性可能会影响2型糖尿病患者冠心病的发生。本研究旨在评估
MTHFR
C677T和A1298C基因突变是否与2型糖尿病患者冠心病的发生风险相关。
方法
本研究一共纳入197例2型糖尿病受试者
其中95例受试者合并冠心病。采用双脱氧链终止法对
MTHFR
C677T和A1298C进行基因分型
并分析比较合并冠心病与不合并冠心病受试者等位基因频率的差异。
结果
合并冠心病2型糖尿病受试者的677T等位基因频率明显高于不合并冠心病的受试者(
P
=0.011)。单倍型频率在合并冠心病与不合并冠心病的2型糖尿病受试者之间无显著的差异。在同型半胱氨酸水平较低的糖尿病受试者中(≤15μmol/L)
携带677T等位基因的受试者发生冠心病风险更高(
P
=0.006)
而在同型半胱氨酸水平较高的糖尿病受试者中(
>
15μmol/L)
MTHFR
基因多态性对冠心病的发生风险无影响(
P
=0.491)。
结论
MTHFR
C677T基因多态性与糖尿病患者发生冠心病的风险相关
对于具有正常同型半胱氨酸水平的中国糖尿病人群
其可作为预测冠心病风险的有效标志物。
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 patients. The purpose of this study was to evaluate whether
MTHFR
C677T and A1298C mutations are associated with the risk of CHD in T2DM patients.
Methods
A total of 197 subjects with T2DM were studied
of which 95 patients with CHD. The genotypes of
MTHFR
C677T and A1298C were analyzed by using dideoxy chain-termination method
and compared between patients with CHD and those without CHD.
Results
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 CHD. Furthermore
the 677T allele was associated with a higher risk of CHD development in diabetic patients with lower homocysteine (Hcy) levels (≤15 μmol/L) (
P
=0.006)
while no effect of
MTHFR
gene polymorphism on the incidence of CHD was found in patients with higher Hcy 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 Hcy levels.
Chen L , Magliano DJ , Zimmet PZ . The worldwide epidemiology of type 2 diabetes mellitus-present and future perspectives . Nat Rev Endocrinol 2011 ; 8 ( 4 ): 228 - 36 . doi: 10.1038/nrendo.2011.183 1001-9294-36-2-103/nrendo.2011.183 . DOI: 10.1038/nrendo.2011.183 http://doi.org/10.1038/nrendo.2011.183
International Diabetes Federation Diabetes Atlas Group . Update of mortality attributable to diabetes for the IDF Diabetes Atlas: estimates for the year 2013 . Diabetes Res Clin Pract 2015 ; 109 ( 3 ): 461 - 5 . doi: 10.1016/j.diabres.2015.05.037 1001-9294-36-2-103/j.diabres.2015.05.037 . DOI: 10.1016/j.diabres.2015.05.037 http://doi.org/10.1016/j.diabres.2015.05.037 https://linkinghub.elsevier.com/retrieve/pii/S0168822715002673 https://linkinghub.elsevier.com/retrieve/pii/S0168822715002673
American Diabetes Association . Diagnosis and Classification of Diabetes Mellitus . Diabetes Care 2004 ; 27 Suppl 1 : S5 - S10 . doi: 10.2337/diacare.27.2007.s5 1001-9294-36-2-103/diacare.27.2007.s5 . DOI: 10.2337/diacare.27.2007.s5 http://doi.org/10.2337/diacare.27.2007.s5 http://care.diabetesjournals.org/cgi/doi/10.2337/diacare.27.2007.S5 http://care.diabetesjournals.org/cgi/doi/10.2337/diacare.27.2007.S5
Brownlee M . Biochemistry and molecular cell biology of diabetic complications . Nature 2001 ; 414 ( 6865 ): 813 - 20 . doi: 10.1038/414813a 1001-9294-36-2-103/414813a . DOI: 10.1038/414813a http://doi.org/10.1038/414813a
Rizvi S , Raza ST , Mahdi F . Association of genetic variants with diabetic nephropathy . World J Diabetes 2014 ; 5 ( 6 ): 809 - 16 . doi: 10.4239/wjd.v5.i6.809 1001-9294-36-2-103/wjd.v5.i6.809 . DOI: 10.4239/wjd.v5.i6.809 http://doi.org/10.4239/wjd.v5.i6.809 http://www.wjgnet.com/1948-9358/full/v5/i6/809.htm http://www.wjgnet.com/1948-9358/full/v5/i6/809.htm
Sun J , Xu Y , Zhu Y , et al . Methylenetetrahydrofolate reductase gene polymorphism, homocysteine and risk of macroangiopathy in type 2 diabetes mellitus . J Endocrinol Invest 2006 ; 29 ( 9 ): 814 - 20 . doi: 10.1007/BF03347376 1001-9294-36-2-103/BF03347376 . DOI: 10.1007/BF03347376 http://doi.org/10.1007/BF03347376 http://link.springer.com/10.1007/BF03347376 http://link.springer.com/10.1007/BF03347376
Fekih-Mrissa N , Mrad M , Ibrahim H , et al . Methylenetetrahydrofolate reductase ( MTHFR ) (C677T and A1298C) polymorphisms and vascular complications in patients with type 2 diabetes . Can J Diabetes 2017 ; 41 ( 4 ): 366 - 71 . doi: 10.1016/j.jcjd.2016.11.007 1001-9294-36-2-103/j.jcjd.2016.11.007 . DOI: S1499-2671(16)30784-5 http://doi.org/S1499-2671(16)30784-5
Frosst P , Blom HJ , Milos R , et al . A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase . Nat Genet 1995 ; 10 ( 1 ): 111 - 3 . doi: 10.1038/ng0595-111 1001-9294-36-2-103/ng0595-111 . DOI: 10.1038/ng0595-111 http://doi.org/10.1038/ng0595-111
Harmon DL , Woodside JV , Yarnell JW , et al . The common ‘thermolabile’ variant of methylene tetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia . QJM 1996 ; 89 ( 8 ): 571 - 7 . doi: 10.1093/qjmed/89.8.571 1001-9294-36-2-103/qjmed/89.8.571 . DOI: 10.1093/qjmed/89.8.571 http://doi.org/10.1093/qjmed/89.8.571 https://academic.oup.com/qjmed/article-lookup/doi/10.1093/qjmed/89.8.571 https://academic.oup.com/qjmed/article-lookup/doi/10.1093/qjmed/89.8.571
van der Put NM , Gabreëls F , Stevens EM , et al . A second common mutation in the methylenetetrahydrofolate reductase gene: an additional risk factor for neural-tube defects? Am J Hum Genet 1998 ; 62 ( 5 ): 1044 - 51 . doi: 10.1086/301825 1001-9294-36-2-103/301825 . DOI: 10.1086/301825 http://doi.org/10.1086/301825
van der Put NM , Blom HJ . Neural tube defects and a disturbed folate dependent homocysteine metabolism . Eur J Obstet Gynecol Reprod Biol 2000 ; 92 ( 1 ): 57 - 61 . doi: 10.1016/s0301-2115(00)00426-7 1001-9294-36-2-103/s0301-2115(00)00426-7 . DOI: 10.1016/s0301-2115(00)00426-7 http://doi.org/10.1016/s0301-2115(00)00426-7
Hankey GJ , Eikelboom JW . Homocysteine and vascular disease . Lancet 1999 ; 354 ( 9176 ): 407 - 13 . doi: 10.1016/S0140-6736(98)11058-9 1001-9294-36-2-103/S0140-6736(98)11058-9 . DOI: 10.1016/S0140-6736(98)11058-9 http://doi.org/10.1016/S0140-6736(98)11058-9
Stehouwer CD , Weijenberg MP , van den Berg M , et al Serum homocysteine and risk of coronary heart disease and cerebrovascular disease in elderly men: a 10-year follow-up . Arterioscler Thromb Vasc Biol 1998 ; 18 ( 12 ): 1895 - 901 . doi: 10.1161/01.atv.18.12.1895 1001-9294-36-2-103/01.atv.18.12.1895 . DOI: 10.1161/01.atv.18.12.1895 http://doi.org/10.1161/01.atv.18.12.1895 https://www.ahajournals.org/doi/10.1161/01.ATV.18.12.1895 https://www.ahajournals.org/doi/10.1161/01.ATV.18.12.1895
Aso Y , Yoshida N , Okumura K , et al . Coagulation and inflammation in overt diabetic nephropathy: association with hyperhomocysteinemia . Clin Chim Acta 2004 ; 348 ( 1-2 ): 139 - 45 . doi: 10.1016/j.cccn.2004.05.006 1001-9294-36-2-103/j.cccn.2004.05.006 . DOI: 10.1016/j.cccn.2004.05.006 http://doi.org/10.1016/j.cccn.2004.05.006 https://linkinghub.elsevier.com/retrieve/pii/S0009898104002384 https://linkinghub.elsevier.com/retrieve/pii/S0009898104002384
Doupis J , Eleftheriadou I , Kokkinos A , et al . Acute hyperhomocysteinemia impairs endothelium function in subjects with type 2 diabetes mellitus . Exp Clin Endocrinol Diabetes 2010 ; 118 ( 7 ): 453 - 8 . doi: 10.1055/s-0030-1248290 1001-9294-36-2-103/s-0030-1248290 . DOI: 10.1055/s-0030-1248290 http://doi.org/10.1055/s-0030-1248290 http://www.thieme-connect.de/DOI/DOI?10.1055/s-0030-1248290 http://www.thieme-connect.de/DOI/DOI?10.1055/s-0030-1248290
Mtiraoui N , Ezzidi I , Chaieb M , et al . MTHFR C677T and A1298C gene polymorphisms and hyperhomocysteinemia as risk factors of diabetic nephropathy in type 2 diabetes patients . Diabetes Res Clin Pract 2007 ; 75 ( 1 ): 99 - 106 . doi: 10.1016/j.diabres.2006.05.018 1001-9294-36-2-103/j.diabres.2006.05.018 . DOI: 10.1016/j.diabres.2006.05.018 http://doi.org/10.1016/j.diabres.2006.05.018 https://linkinghub.elsevier.com/retrieve/pii/S016882270600235X https://linkinghub.elsevier.com/retrieve/pii/S016882270600235X
Sun J , Xu Y , Zhu Y , et al . The relationship between MTHFR gene polymorphisms, plasma homocysteine levels and diabetic retinopathy in type 2 diabetes mellitus . Chin Med J (Engl) 2003 ; 116 ( 1 ): 145 - 7 .
Cao H , Huang DF , Mao L , et al . Association of homocysteine, methylenetetrahydrofolate reductase gene polymorphism with type 2 diabetes mellitus with cerebral infarction . Chin J Dis Control Prev 2010 ; 14 ( 3 ): 196 - 8 . (In Chinese)
Luo D , Yan SK , Cheng XQ , et al . Levels of homocysteine and polymorphisms of homocysteine metabolism related enzymes in patients with type 2 diabetes mellitus and coronary heart disease . J Hygiene Res 2009 ; 38 ( 1 ): 39 - 42 . (In Chinese)
Sun J , Xu Y , Xue J , et al . Methylenetetrahydrofolate reductase polymorphism associated with susceptibility to coronary heart disease in Chinese type 2 diabetic patients . Mol Cell Endocrinol 2005 ; 229 ( 1-2 ): 95 - 101 . doi: 10.1016/j.mce.2004.09.003 1001-9294-36-2-103/j.mce.2004.09.003 . DOI: 10.1016/j.mce.2004.09.003 http://doi.org/10.1016/j.mce.2004.09.003 https://linkinghub.elsevier.com/retrieve/pii/S0303720704003570 https://linkinghub.elsevier.com/retrieve/pii/S0303720704003570
Wu XF , Cheng LX , He MA . Association between polymorphism of methylenetetrahydrofolate reductase C677T and coronary heart disease . Acta Med Univ Sci Technol Huazhong 2009 ; 38 ( 3 ): 296 - 300 . doi: 10.3870/ j.issn.1672-0741.2009.03.004. (In Chinese 1001-9294-36-2-103/ j.issn.1672-0741.2009.03.004. (In Chinese) ) DOI: 10.3870/ j.issn.1672-0741.2009.03.004. (In Chinese http://doi.org/10.3870/ j.issn.1672-0741.2009.03.004. (In Chinese
Zhao XD , Wang L . The relationship of plasma homocysteine and the polymorphism of MTHFR gene with brain infaction in type 2 diabetes mellitus . Chin J Diabetes 2015 ; 23 ( 2 ): 107 - 9 . doi: 10.3969/j.issn.1006-6187.2015.02.003. (In Chinese 1001-9294-36-2-103/j.issn.1006-6187.2015.02.003. (In Chinese) ) DOI: 10.3969/j.issn.1006-6187.2015.02.003. (In Chinese http://doi.org/10.3969/j.issn.1006-6187.2015.02.003. (In Chinese
Wang GB , Shen QD , ping LD . Correlation between homocysteine levels and MTHFR C677T gene polymorphism of cerebral infarction . J Med Res 2017 ; 46 ( 5 ): 154 - 8 . doi: 10.11969/j.issn.1673-548X.2017.05.038. (In Chinese 1001-9294-36-2-103/j.issn.1673-548X.2017.05.038. (In Chinese) ) DOI: 10.11969/j.issn.1673-548X.2017.05.038. (In Chinese http://doi.org/10.11969/j.issn.1673-548X.2017.05.038. (In Chinese
Mata-Cases M , Artola S , Escalada J , et al . Consensus on the detection and management of prediabetes. Consensus and Clinical Guidelines Working Group of the Spanish Diabetes Society . Rev Clin Esp 2015 ; 215 ( 2 ): 117 - 29 . doi: 10.1016/j.rce.2014.10.012 1001-9294-36-2-103/j.rce.2014.10.012 . DOI: 10.1016/j.rce.2014.10.012 http://doi.org/10.1016/j.rce.2014.10.012
Cardiovascular Specialty Group in the First National Internal Medicine Conference . Recommendations on the naming and diagnostic criteria of coronary heart disease . Chin J Int Med 1981 ; 20 ( 4 ): 253 - 5 . (In Chinese)
Dzida G , Biłan A , Golon-Siekierska P , et al . Methylenetetrahydrofolate reductase gene polymorphism in patients with type 2 diabetes . Pol Arch Med Wewn 2001 ; 106 ( 1 ): 543 - 9 .
Beneš P , Kaňková K , Mužı́k J , et al . Methylenetetrahydrofolate reductase polymorphism, typeⅡ diabetes mellitus, coronary artery disease, and essential hypertension in the Czech population . Mol Genet Metab 2001 ; 73 ( 2 ): 188 - 95 . doi: 10.1006/mgme.2001.3188 1001-9294-36-2-103/mgme.2001.3188 . DOI: 10.1006/mgme.2001.3188 http://doi.org/10.1006/mgme.2001.3188 https://linkinghub.elsevier.com/retrieve/pii/S1096719201931889 https://linkinghub.elsevier.com/retrieve/pii/S1096719201931889
Settin A , El-Baz R , Ismaeel A , et al . Association of ACE and MTHFR genetic polymorphisms with type 2 diabetes mellitus: susceptibility and complications . J Renin Angiotensin Aldosterone Syst 2015 ; 16 ( 4 ): 838 - 43 . doi: 10.1177/1470320313516172 1001-9294-36-2-103/1470320313516172 . DOI: 10.1177/1470320313516172 http://doi.org/10.1177/1470320313516172
Böger CA , Stubanus M , Haak T , et al . Effect of MTHFR C677T genotype on survival in type 2 diabetes patients with end-stage diabetic nephropathy . Nephrol Dial Transplant 2007 ; 22 ( 1 ): 154 - 62 . doi: 10.1093/ndt/gfl512 1001-9294-36-2-103/ndt/gfl512 . DOI: 10.1093/ndt/gfl512 http://doi.org/10.1093/ndt/gfl512 https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfl512 https://academic.oup.com/ndt/article-lookup/doi/10.1093/ndt/gfl512
Brulhart MC , Dussoix P , Ruiz J , et al . The (Ala-Val) mutation of methylenetetrahydrofolate reductase as a genetic risk factor for vascular disease in non-insulin-dependent diabetic patients . Am J Hum Genet 1997 ; 60 ( 1 ): 228 - 9 .
Wirta V , Huang XH , Wirta O , et al . Mutation C677T of methylenetetrahydrofolate reductase gene is not associated with coronary artery disease, but possibly with albuminuria, in type 2 diabetic patients . Clin Chem Lab Med 1998 ; 36 ( 8 ): 625 - 8 . doi: 10.1515/CCLM.1998.109 1001-9294-36-2-103/CCLM.1998.109 . DOI: 10.1515/CCLM.1998.109 http://doi.org/10.1515/CCLM.1998.109
Audelin MC , Genest JJ . Homocysteine and cardiovascular disease in diabetes mellitus . Atherosclerosis 2001 ; 159 ( 2 ): 497 - 511 . doi: 10.1016/s0021-9150(01)00531-7 1001-9294-36-2-103/s0021-9150(01)00531-7 . DOI: 10.1016/s0021-9150(01)00531-7 http://doi.org/10.1016/s0021-9150(01)00531-7
Hoogeveen EK , Kostense PJ , Beks PJ , et al . Hyperhomocysteinemia is associated with an increased risk of cardiovascular disease, especially in non-insulin-dependent diabetes mellitus: a population-based study . Arterioscler Thromb Vasc Biol 1998 ; 18 ( 1 ): 133 - 8 . doi: 10.1161/01.atv.18.1.133 1001-9294-36-2-103/01.atv.18.1.133 . DOI: 10.1161/01.atv.18.1.133 http://doi.org/10.1161/01.atv.18.1.133 https://www.ahajournals.org/doi/10.1161/01.ATV.18.1.133 https://www.ahajournals.org/doi/10.1161/01.ATV.18.1.133
Yeromenko Y , Lavie L , Levy Y . Homocysteine and cardiovascular risk in patients with diabetes mellitus . Nutr Metab Cardiovasc Dis 2001 ; 11 ( 2 ): 108 - 16 .
关联资源
相关文章
相关作者
相关机构
京公网安备11010802024621