허혈성 뇌졸중 환자에서 MTHFR C677T 단일 염기 다형성이 비타민에 의한 혈장 호모시스테인 농도 감소에 미치는 영향 = The Effect of MTHFR C677T Single Nucleotide Polymorphism on Plasma Homocysteine Lowering Therapy with Vitamuns in the Ischemic Stroke Patients

다국어 초록 (Multilingual Abstract)

Background: C677T single nucleotide polymorphism (SNP) of Methylentetrahydrofolate reductase (MTHFR) has been known to be associated with plasma homocysteine (Hcy) levels, which is an independent risk factor for stroke. However, recent large clinical trials did not show any benefits of Hcy lowering therapy with vitamins on the prevention of stroke. We hypothesized that the Hcy lowering effect by vitamins would be different according to the MTHFR C677T SNP types (CC, CT or TT), which may influence the benefits of vitamins by Hcy lowering on stroke prevention.
Methods: The authors retrospectively studied acute stroke patients with information of the genotype of MTHFR and serial levels of Hcy during a recent 4 year period (July 2002 . Dec 2005). Vitamins (folic acid 1 mg, and/or cobalamin 750 μg and pyridoxine 75 mg) were prescribed to the patients whose basal plasma Hcy levels were above 12 umol/L.
Results: Among 172 patients, 68 patients took vitamins. The mean basal Hcy level was significantly higher in the TT type than the others, and was decreased by vitamin therapy. Distribution of homocysteine grading (normal, intermediate or high) in follow up was not significantly different according to these SNP types.
Conclusions: The Hcy lowering effect by vitamins was not different by MTHFR genetic polymorphism. Considering the higher prevalence of certain gene types in stroke and our study results, genetic factors such as MTHFR polymorphism may play an important role on the development of stroke rather than the plasma Hcy levels.

참고문헌 (Reference)

1 "ine concentration as a possible independent risk factor for stroke. Stroke 1990" mali (mali): 572-576,

2 "and folate nutritional status in men with hyperhomocysteinemia. Am J Clin Nutr 1993" 47-6 53,

3 "an independent risk factor for vascular disease. N Engl J Med 1991" 1149-1155,

4 "Vitamins as homocysteine-lowering agents" 126 : 1276-1280, 1996

5 "Vitamin Intervention for Stroke Prevention (VISP) trial: rationale and design" 20 : 16-25, 2001

6 "Total plasma homocysteine and cardiovascular risk profile. The Hordaland Homocysteine Study" 274 : 1526-1533, 1995

7 "Relation of plasma homocyst(e)ine to cerebral infarction and cerebral atherosclerosis" 29 : 2478-2483, 1998

8 "Polymorphisms of methylenetetrahydrofolate reductase and other enzymes: metabolic significance, risks and impact on folate requirement" 129 : 919-922, 1999

9 "Plasma homocysteine as a risk factor for vascular disease. The European Concerted Action Project" 277 : 1775-1781, 1997

10 "Metabolism of homocysteine and its relationship with cardiovascular disease" 18 : 75-87, 2004

11 "Lowering homocysteine in patients with ischemic stroke to prevent recurrent stroke, myocardial infarction, and death: the Vitamin Intervention for Stroke Prevention (VISP) randomized controlled trial" 291 : 565-575, 2004

12 "Hyperhomocysteinemia and the endocrine system: implications for atherosclerosis and thrombosis" 20 : 738-759, 1999

13 "Homocysteine metabolism" 19 : 217-246, 1999

14 "Homocysteine lowering with folic acid and B vitamins in vascular disease" 354 : 1567-1577, 2006

15 "Homocysteine and thrombotic disease" 90 : 1-11, 1997

16 "Homocysteine and risk of recurrent stroke" 34 : 1258-1261, 2003

17 "Homocysteine and risk of ischemic heart disease and stroke: a meta-analysis" 288 : 2015-2022, 2002

18 "Homocysteine and neurologic disease" 57 : 1422-1427, 2000

19 "Grix A. Intermediate hyperhomocysteinemia resulting from compound heterozygosity of methylenetetrahydrofolate reductase mutations. Am J Hum Genet 1991" 546-551,

20 "Elevated homocysteine levels in alcohol withdrawal" 35 : 351-354, 2000

21 "Determinants of hyperhomocysteinemia: a matter of nature and nurture" 64 : 641-642, 1996

22 "Congenital thrombophilic states associated with venous thrombosis: a qualitative overview and proposed classification system" 138 : 128-134, 2003

23 "Common methylenetetrahydrofolate reductase gene mutation leads to hyperhomocysteinemia but not to vascular disease: the result of a meta-analysis" 98 : 2520-2526, 1998