伴血脂异常2型糖尿病患者亚甲基四氢叶酸还原酶基因多态性与血浆同型半胱氨酸水平的相关性

尹影; 李蕊; 李晓黎; 吴坤荣; 李玲; 徐曰东; 廖琳; 杨蕊; 李妍

doi:10.24920/003532

Your Location：

Home >

Browse articles >

伴血脂异常2型糖尿病患者亚甲基四氢叶酸还原酶基因多态性与血浆同型半胱氨酸水平的相关性

中国医学科学杂志（英文版） 2020年35卷第1期页码：85-91

Original Article | Updated：2024-04-10

- 伴血脂异常2型糖尿病患者亚甲基四氢叶酸还原酶基因多态性与血浆同型半胱氨酸水平的相关性
- Affiliations：
  
  1School of Pharmaceutical Sciences, Shandong First Medical University & Shandong Academy of Medical Sciences, Tai’an, Shandong 271000, China
  2School of Pharmaceutical Sciences, Shandong University, Jinan 250012, China
  3Department of Pharmacy, Shandong Provincial Qianfoshan Hospital, Jinan 250014, China
  4Department of Endocrinology, Shandong Provincial Qianfoshan Hospital, Jinan 250014, China
- Author bio：
  
  * Tel: 86-531-89268352, E-mail: li_xyan@126.com
- Funds：
  
  National Key Development Plan for Precision Medicine Research(2017YFC0910004);Jinan Science Project(201602171);Jinan Science and Technology Plan Project(201503009)
- DOI：10.24920/003532
  中图分类号：
- 收稿日期：2019-05-12，
  
  网络出版日期：2020-03-31，
  
  纸质出版日期：2020-03-07
- Accepted：
Scan QR Code
尹影, 李蕊, 李晓黎, 等. 伴血脂异常2型糖尿病患者亚甲基四氢叶酸还原酶基因多态性与血浆同型半胱氨酸水平的相关性[J]. 中国医学科学杂志（英文版）, 2020,35(1):85-91.

Yin Ying, Li Rui, Li Xiaoli, et al. Association Between Homocysteine Level and Methylenetetrahydrofolate Reductase Gene Polymorphisms in Type 2 Diabetes Accompanied by Dyslipidemia[J]. Chinese medical sciences journal, 2020, 35(1): 85-91.
尹影, 李蕊, 李晓黎, 等. 伴血脂异常2型糖尿病患者亚甲基四氢叶酸还原酶基因多态性与血浆同型半胱氨酸水平的相关性[J]. 中国医学科学杂志（英文版）, 2020,35(1):85-91. DOI： 10.24920/003532.

Yin Ying, Li Rui, Li Xiaoli, et al. Association Between Homocysteine Level and Methylenetetrahydrofolate Reductase Gene Polymorphisms in Type 2 Diabetes Accompanied by Dyslipidemia[J]. Chinese medical sciences journal, 2020, 35(1): 85-91. DOI： 10.24920/003532.

摘要

目的

探讨中国汉族血脂异常2型糖尿病（T2DM）患者血浆总同型半胱氨酸（tHcy）水平与亚甲基四氢叶酸还原酶（MTHFR）基因C677T和A1298C多态性的相关性。

方法

研究纳入179例中国汉族T2DM患者

采用sanger双脱氧链终止法检测MTHFR C677T和A1298C的基因多态性

采用酶循环法检测血浆tHcy。按照血脂水平将患者分为血脂正常组和异常组

采用卡方检验比较两组MTHFRC677T和A1298C多态性基因型频率和等位基因频率的差异

采用Student's t检验比较两组中携带不同基因型患者血浆tHcy水平的差异。

结果

研究纳入T2DM血脂异常患者82例

T2DM血脂正常患者94例。T2DM患者的MTHFR C677T多态性与tHcy水平之间存在显著相关性（

=2.27

=0.02）。携带MTHFR 677 TT基因型的血脂异常患者的血浆tHcy水平显著高于携带CT+CC基因型患者（13.62±6.97比10.95±3.62 μmol/L

=2.20

=0.03）;而对于血脂正常的患者

携带上述两个等位基因的患者的tHcy水平无显著差异（13.34±6.03比12.04±5.09 μmol/L

=1.08

=0.29）。

结论

MTHFR 677TT基因多态性可能与血脂异常的2型糖尿病患者的血浆tHcy水平升高有关。

Abstract

Objective

To investigate the association between total homocysteine (tHcy) level in plasma and methylenetetrahydrofolate reductase (

MTHFR

) C677T and A1298C genetic polymorphisms in a Chinese Han nationality population with type 2 diabetes mellitus (T2DM) accompanied by dyslipidemia.

Methods

This case-control study enrolled T2DM patients with dyslipidemia and without dyslipidemia respectively. Sanger dideoxy-mediated chain-termination method was used to detect the gene polymorphisms of

MTHFR

C677T and A1298C. Plasma tHcy and lipid levels were measured as well. The genotype frequency and allele frequency between the dyslipidemia and non-dyslipidemia groups were compared by using

Chi-square

test. Plasma tHcy level of T2DM patients who carried the different genotypes was compared by Student’s

test.

Results

Finally

82 T2DM patients with dyslipidemia and 94 ones without dyslipidemia were included in this study. There was a significant correlation between tHcy level and

MTHFR

C677T gene polymorphism in T2DM patients (

=2.27

=0.02). Moreover

the plasma tHcy level in the dyslipidemia patients who carried

MTHFR

677 TT genotype was significantly higher than that in those with CT+CC genotype (13.62±6.97

. 10.95±3.62 μmol/L

=2.20

=0.03); while for patients without dyslipidemia

comparison of the tHcy level between those who carried the above two alleles showed no significantly difference (13.34±6.03

. 12.04±5.09 μmol/L

=1.08

=0.29).

Conclusion

MTHFR

677TT genotype might associate with higher tHcy level in T2DM patients with dyslipidemia.

关键词

Keywords

references

Mottillo S , Filion KB , Genest J , et al . The metabolic syndrome and cardiovascular risk. A systematic review and meta-analysis . J Am Coll Cardiol 2010 ; 56 ( 14 ): 1113 - 32 . doi: 10.1016/j.jacc.2010.05.034 10.1016/j.jacc.2010.05.034 .

Fox CS , Coady S , Sorlie PD , et al . Trends in cardiovascular complications of diabetes . JAMA 2004 ; 292 ( 20 ): 2495 - 9 . doi: 10.1001/jama.292.20.2495 10.1001/jama.292.20.2495 .

Outinen PA , Sood SK , Liaw PC , et al . Characterization of the stress-inducing effects of homocysteine . Biochem J 1998 ; 332 ( 1 ): 213 - 21 .

Pollex RL , Mamakeesick M , Zinman B , et al . Methylenetetrahydrofolate reductase polymorphism 677C>T is associated with peripheral arterial disease in type 2 diabetes . Cardiovasc Diabetol 2005 ; 4 ( 1 ): 17 . doi: 10.1186/1475-2840-4-17 10.1186/1475-2840-4-17 .

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 10.1161/01.ATV.18.1.133 .

Hackam DG . Emerging risk factors for atherosclerotic vascular disease: a critical review of the evidence . JAMA 2003 ; 290 ( 7 ): 932 - 40 . doi: 10.1001/jama.290.7.932 10.1001/jama.290.7.932 .

Klerk M , Verhoef P , Clarke R , et al . MTHFR 677C T polymorphism and risk of coronary heart disease: a meta-analysis . JAMA 2002 ; 288 ( 16 ): 2023 - 31 . doi: 10.1001/jama.288.16.2023 10.1001/jama.288.16.2023 .

Audelin MC , Genest J . Homocysteine and cardiovascular disease in diabetes mellitus . Atherosclerosis 2001 ; 159 : 497 - 511 . doi: 10.1016/s0021-9150(01)00531-7 10.1016/s0021-9150(01)00531-7 .

Harmon DL , Woodside JV , Yarnell JW , et al . The common ‘thermolabile’ variant of methylenetetrahydrofolate reductase is a major determinant of mild hyperhomocysteinaemia . QJM 1996 ; 89 ( 8 ): 571 - 7 . doi: 10.1093/qjmed/89.8.571 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 10.1086/301825 .

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 10.1038/ng0595-111 .

Arnadottir M , Hultberg B , Nilsson-Ehle P , et al . The effect of reduced glomerular filtration rate on plasma total homocysteine concentration . Scand J Clin Lab Invest 1996 ; 56 ( 1 ): 41 - 6 . doi: 10.3109/00365519609088586 10.3109/00365519609088586 .

Rozycka A , Jagodzinski PP , Kozubski W , et al . Homocycsteine level and mechanisms of injury in Parkinson’s disease as related to MTHFR, MTR, THFD1 genes polymorphisms and L-Dopa treatment . Curr Genomics 2013 ; 14 ( 8 ): 534 - 42 . doi: 10.2174/1389202914666131210210559 10.2174/1389202914666131210210559 .

Krumdieck CL , Prince CW . Mechanisms of homocysteine toxicityon connective tissues: implications for the morbidity of aging . J Nutr 2000 ; 130 ( 2S Suppl ): 365S - 8S . doi: 10.1093/jn/130.2.365S 10.1093/jn/130.2.365S .

Haynes WG . Hyperhomocysteinaemia, vascular function and athersclerosis: effects of vitamins . Cadiovasc Drugs Ther 2002 ; 16 ( 5 ): 391 - 9 .

Glueck CJ , Shaw P , Lang JE , et al . Evidence that homocysteine is an independent risk factor for atherosclerosis in hyperlipidemic patients . Am J Cardiol 1995 ; 75 ( 2 ): 132 - 6 . doi: 10.1016/s0002-9149(00)80061-2 10.1016/s0002-9149(00)80061-2 .

Goyette P , Sumner JS , Milos R , et al . Human methylenetetrahydrofolate reductase: isolation of cDNA mapping and mutation identification . Nat Genet 1994 ; 7 ( 4 ): 551 .

Doshi SN , Goodfellow J , Lewis MJ , et al . Homocysteine and endothelial function . Cardiovasc Res 1999 ; 42 ( 3 ): 578 - 82 . doi: 10.1016/s0008-6363(99)00029-2 10.1016/s0008-6363(99)00029-2 .

Hanson NQ , Aras O , Yang F . C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase gene: incidence and effect of combined genotypes on plasma fasting and post-methionine load homocysteine in vascular disease . Clin Chem 2001 ; 47 ( 4 ): 661 - 6 .

Spiridonova MG , Stepanov VA , Pyzyrev VP . Relationship between polymorphism C677T of the methylenetetrahydrofolate reductase gene with clinical symptoms of coronary atherosclerosis . Genetika 2000 ; 36 ( 9 ): 1269 - 73 .

Liang R , Zhou Y , Xie J , et al . Association of C677T gene polymorphisms of methylenetetrahydrofolate reductase and plasma homocysteine level with hyperlipidemia . Nan Fang Yi Ke Da Xue Xue Bao 2014 ; 34 ( 8 ): 1195 - 8 . doi: 10.3969/j.issn.1673-4254.2014.08.25 10.3969/j.issn.1673-4254.2014.08.25 .

Mao Y , Fan YH , Bai J , et al . Polymorphism of methylenetetrahydrofolate reductase and association with diseases . Int J Genetics 1998 ; 15 ( 5 ): 38 - 40 .

Cortese C . MTHFR gene polymorphism, homocysteine and cardiovascular disease . Public Health Nutr 2001 ; 4 ( 2b ): 493 - 7 . doi: 10.1079/PHN2001159 10.1079/PHN2001159 .

Errera FI , Silva ME , Yeh E , et al . Effect of polymorphisms of the MTHFR and APOE genes on susceptibility to diabetes and severity of diabetic retinopathy in Brazilian patients . Braz J Med Biol Res 2006 ; 39 ( 7 ): 883 - 8 . doi: 10.1590/S0100-879X2006000700005 10.1590/S0100-879X2006000700005 .

Benrahma H , Abidi O , Melouk L , et al . Association of the C677T polymorphism in the human methylenetetrahydrofolate reductase (MTHFR) gene with the genetic predisposition for type 2 diabetes mellitus in a Moroccan population . Genet Test Mol Biomarkers 2012 ; 16 ( 5 ): 383 - 7 . doi: 10.1089/gtmb.2011.0179 10.1089/gtmb.2011.0179 .

Sun J , Xu Y , Zhu Y . Genetic polymorphism of methylenetetrahydrofolate reductase as a risk factor for diabetic nephropathy in Chinese type 2 diabetic patients . Diabetes Res Clin Pract 2004 ; 64 ( 3 ): 185 - 90 . doi: 10.1016/j.diabres.2003.10.022 10.1016/j.diabres.2003.10.022 .

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 10.1055/s-0030-1248290 .

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 10.1016/j.cccn.2004.05.006 .

Araki A , Sako Y , Ito H . Plasma homocysteine concentrations in Japanese patients with non-insulin-dependent diabetes mellitus: effect of parenteral methylcobalamin treatment . Atherosclerosis 1993 ; 103 ( 2 ): 149 - 57 . doi: 10.1016/0021-9150(93)90258-v 10.1016/0021-9150(93)90258-v .

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 10.1016/j.jcjd.2016.11.007 .

Sun JZ , Xu Y , Lu H . Polymorphism of the methylenetetrahydrofolate reductase gene association with homocysteine and ischemic stroke in type 2 diabetes . Neurol India 2009 ; 57 ( 5 ): 589 - 93 . doi: 10.4103/0028-3886.57808 10.4103/0028-3886.57808 .

浏览量

645

Downloads

CSCD

文章被引用时，请邮件提醒。

Submit

关联资源

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

Association between Air Pollution and Type 2 Diabetes Mellitus in Developing Countries: A Systematic Review and Meta-Analysis

Methylenetrahydrofolate Reductase Gene C677T Polymorphism and Diabetic Retinopathy: a Meta-Analysis

Abnormal Alterations of Cortical Thickness in 16 Patients with Type 2 Diabetes Mellitus: A Pilot MRI Study^△