Genetic polymorphisms involved in folate metabolism and concentrations of methylmalonic acid and folate on plasma homocysteine and risk of coronary artery disease

被引：110

作者：

Biselli, Patricia Matos ^{[1
]}

Guerzoni, Alexandre Rodrigues ^{[1
]}

de Godoy, Moacir Fernandes ^{[2
]}

Eberlin, Marcos Nogueira ^{[3
]}

Haddad, Renato ^{[3
]}

Carvalho, Valdemir Melechco ^{[4
]}

Vannucchi, Helio ^{[6
]}

Pavarino-Bertelli, Erika Cristina ^{[1
,5
]}

Goloni-Bertollo, Eny Maria ^{[1
,5
]}

机构：

[1] Sao Jose do Rio Preto Med Sch FAMERP, Genet & Mol Biol Res Unit UPGEM, BR-15090000 Sao Jose Do Rio Preto, SP, Brazil

[2] Sao Jose do Rio Preto Med Sch FAMERP, Dept Cardiol, BR-15090000 Sao Jose Do Rio Preto, SP, Brazil

[3] State Univ Campinas UNICAMP, Dept Chem, Campinas, SP, Brazil

[4] Fleury Res Inst, Sao Paulo, Brazil

[5] Sao Jose do Rio Preto Med Sch FAMERP, Dept Mol Biol, BR-15090000 Sao Jose Do Rio Preto, SP, Brazil

[6] Univ Sao Paulo, Dept Clin Med, BR-14049 Ribeirao Preto, Brazil

来源：

JOURNAL OF THROMBOSIS AND THROMBOLYSIS | 2010年 / 29卷 / 01期

基金：

巴西圣保罗研究基金会;

关键词：

Coronary artery disease; Homocysteine; Genetic polymorphisms; Methylmalonic acid; METHYLENETETRAHYDROFOLATE REDUCTASE GENE; METHIONINE SYNTHASE; SERUM HOMOCYSTEINE; C677T MUTATION; FOLIC-ACID; MTHFR; HYPERHOMOCYSTEINEMIA; VITAMIN-B-12; ASSOCIATION; A1298C;

D O I：

10.1007/s11239-009-0321-7

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objectives Alterations in the enzymes involved in homocysteine (Hcy) metabolism or vitamin deficiency could play a role in coronary artery disease (CAD) development. This study investigated the influence of MTHFR and MTR gene polymorphisms, plasma folate and MMA on Hcy concentrations and CAD development. MMA and folate concentrations were also investigated according to the polymorphisms. Methods Two hundred and eighty-three unrelated Caucasian individuals undergoing coronary angiography (175 with CAD and 108 non-CAD) were assessed in a case-control study. Plasma Hcy and MMA were measured by liquid chromatography/tandem mass spectrometry. Plasma folate was measured by competitive immunoassay. Dietary intake was evaluated using a nutritional questionnaire. Polymorphisms MTHFR and MTR were investigated by polymerase chain reaction (PCR) followed by enzyme digestion or allele-specific PCR. Results Hcy mean concentrations were higher in CAD patients compared to controls, but below statistical significance (P = 0.246). Increased MMA mean concentrations were frequently observed in the CAD group (P = 0.048). Individuals with MMA concentrations > 0.5 mu mol/l (vitamin B-12 deficiency) were found only in the CAD group (P = 0.004). A positive correlation between MMA and Hcy mean concentrations was observed in both groups, CAD (P = 0.001) and non-CAD (P = 0.020). MMA mean concentrations were significantly higher in patients with hyperhomocysteinemia in both groups, CAD and non-CAD (P = 0.0063 and P = 0.013, respectively). Folate mean concentration was significantly lower in carriers of the wild-type MTHFR 1298AA genotype (P = 0.010). Conclusion Our results suggest a correlation between the MTHFR A1298C polymorphism and plasma folate concentration. Vitamin B-12 deficiency, reflected by increased MMA concentration, is an important risk factor for the development both of hyperhomocysteinemia and CAD.

引用

页码：32 / 40

页数：9

共 57 条

[1] MOLECULAR INTERACTION OF [2,3-C-14] ACRYLONITRILE WITH DNA IN GASTRIC TISSUE OF RAT [J].

ABDELRAHMAN, SZ ;

NOURALDEEN, AM ;

AHMED, AE .

JOURNAL OF BIOCHEMICAL TOXICOLOGY, 1994, 9 (04) :191-198

[2]

Abu-Amero KK, 2003, ARCH PATHOL LAB MED, V127, P1349

[3]

[Anonymous], 1998, DIET REF INT THIAM R

[4]

Arruda VR, 1998, AM J MED GENET, V78, P332, DOI 10.1002/(SICI)1096-8628(19980724)78:4<332::AID-AJMG5>3.0.CO

[5]

2-N

[6] Role of hyperhomocysteinemia in endothelial dysfunction and atherothrombotic disease [J].

Austin, RC ;

Lentz, SR ;

Werstuck, GH .

CELL DEATH AND DIFFERENTIATION, 2004, 11 (Suppl 1) :S56-S64

[7] A common mutation in the methylenetetrahydrofolate reductase gene is associated with an accumulation of formylated tetrahydrofolates in red blood cells [J].

Bagley, PJ ;

Selhub, J .

PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 1998, 95 (22) :13217-13220

[8] Plasma pyridoxal phosphate and pyridoxic acid and their relationship to plasma homocysteine in a representative sample of British men and women aged 65 years and over [J].

Bates, CJ ;

Pentieva, KD ;

Prentice, A ;

Mansoor, MA ;

Finch, S .

BRITISH JOURNAL OF NUTRITION, 1999, 81 (03) :191-201

[9] The A677V methylenetetrahydrofolate reductase gene polymorphism and carotid atherosclerosis [J].

Bova, I ;

Chapman, J ;

Sylantiev, C ;

Korczyn, AD ;

Bornstein, NM .

STROKE, 1999, 30 (10) :2180-2182

[10] Potential cardiovascular risk factors in chronic kidney disease:: AGEs, total homocysteine and metabolites, and the C-reactive protein [J].

Busch, M ;

Franke, S ;

Müller, A ;

Wolf, M ;

Gerth, J ;

Ott, U ;

Niwa, T ;

Stein, G .

KIDNEY INTERNATIONAL, 2004, 66 (01) :338-347

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