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

被引：0
作者：
Patrícia Matos Biselli
Alexandre Rodrigues Guerzoni
Moacir Fernandes de Godoy
Marcos Nogueira Eberlin
Renato Haddad
Valdemir Melechco Carvalho
Hélio Vannucchi
Érika Cristina Pavarino-Bertelli
Eny Maria Goloni-Bertollo
机构：
[1] Genetics and Molecular Biology Research Unit—UPGEM,Department of Cardiology
[2] São José do Rio Preto Medical School—FAMERP,Department of Chemistry
[3] São José do Rio Preto Medical School—FAMERP,Department of Clinical Medicine
[4] State University of Campinas—UNICAMP,Department of Molecular Biology
[5] Fleury Research Institute,undefined
[6] University of São Paulo Medical School—USP,undefined
[7] São José do Rio Preto Medical School—FAMERP,undefined
来源：
Journal of Thrombosis and Thrombolysis | 2010年 / 29卷
关键词：
Coronary artery disease; Homocysteine; Genetic polymorphisms; Methylmalonic acid;
D O I：
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学科分类号：
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 μmol/l (vitamin B12 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 B12 deficiency, reflected by increased MMA concentration, is an important risk factor for the development both of hyperhomocysteinemia and CAD.
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页码：32 / 40
页数：8
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