scholarly journals Methylenetetrahydrofolate reductase gene polymorphism and its association with coronary artery disease

2007 ◽  
Vol 125 (1) ◽  
pp. 4-8 ◽  
Author(s):  
Alexandre Rodrigues Guerzoni ◽  
Érika Cristina Pavarino-Bertelli ◽  
Moacir Fernandes de Godoy ◽  
Carla Renata Graça ◽  
Patrícia Matos Biselli ◽  
...  

CONTEXT AND OBJECTIVE: Obstructive coronary artery disease (CAD) is characterized by the deposition of atherosclerotic plaque on the coronary artery wall. Its manifestations depend on interactions between environmental and genetic risk factors. The aim of this work was to analyze the frequency of methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in patients with CAD and its association with plasma homocysteine levels. Risk factors for CAD were also evaluated. DESIGN AND SETTING: Retrospective with blind quantitative analysis, at Hospital de Base, Faculdade de Medicina de São José do Rio Preto. METHODS: One hundred and twenty-seven individuals were studied. All completed a questionnaire to analyze risk factors for CAD. MTHFR polymorphism was investigated by restriction fragment length analysis and correlated with the number of affected arteries and degree of arterial obstruction determined by coronary cineangiography, and with plasma homocysteine levels measured by liquid chromatography/sequential mass spectrometry. RESULTS: Smoking (p = 0.02) and high-density lipoprotein cholesterol (p = 0.01) were associated with CAD. The C allele was the most prevalent in patients (0.61) and controls (0.66). There was no correlation between MTHFR/C677T polymorphism and plasma homocysteine levels. However, in patients with the TT genotype there was a correlation with the prevalence of coronary obstruction greater than 95% (p = 0.02) and the presence of two affected arteries (p = 0.04). CONCLUSIONS: The TT genotype is associated with coronary artery obstruction greater than 95% and the presence of two affected arteries. This confirms the relationship between genetic variants in specific patient subgroups and cardiovascular diseases.

2007 ◽  
Vol 2007 ◽  
pp. 1-9 ◽  
Author(s):  
Nawal Bennouar ◽  
Abdellatif Allami ◽  
Houssine Azeddoug ◽  
Abdenbi Bendris ◽  
Abdelilah Laraqui ◽  
...  

Increased plasma total homocysteine (tHcy) levels have been shown to be a risk factor for coronary artery disease (CAD). The common methylenetetrahydrofolate reductase C677T (MTHFR C677T) polymorphism has been reported to be a strong predictor of mild hyperhomocysteinaemia (HHcy). We assessed whether this mutation was associated with increased risk of CAD and plasma levels of tHcy. We also evaluated interactions between this polymorphism, mild elevated tHcy levels and conventional risk factors of CAD.Method. Using PCR-RFLP analysis, we studied the frequency of the C677T genotypes and its effect on CAD and on tHcy concentrations in 400 subjects without and with CAD angiographically confirmed. There were 210 subjects with CAD and 190 subjects without CAD.Results. The frequencies of the C677T genotypes were 53%(59.5%in controls versus 48.1%in cases), 34.8%(32.1 in controls versus 37.1 in cases), and 11.8%(8.4%in controls versus 14.8%in cases), respectively, for 677CC, 677CT, and 677TT. The genotype frequencies were significantly different between case and control groups (P<.05). The 677T allele enhances the risk of CAD associated to HHcy (P<.01). In multivariate analysis models, MTHFR C677T polymorphism effect on CAD was masked by other risk factors. HHcy was only and independently influenced by MTHFR polymorphism and smoking habits, and it is a strong predictor of CAD independently of conventional risk factors.Conclusion. Our data suggest that HHcy is strongly and independently associated to CAD risk increase; and MTHFR C677T polymorphism and smoking habits were the main predictors of tHcy levels. The CAD risk increase is mainly associated with mild HHcy in 677TT, whereas in 677CT and 677CC it is mainly associated with the conventional risk factors.


2005 ◽  
Vol 93 (02) ◽  
pp. 346-350 ◽  
Author(s):  
Anetta Undas ◽  
Milosz Jankowski ◽  
Magdalena Twardowska ◽  
Agnieszka Padjas ◽  
Hieronim Jakubowski ◽  
...  

Summary N-homocysteinylated (Nε-Hcy) proteins and corresponding antibodies have recently been discovered in humans and animals. Increased autoimmune response to Nε -Hcy-proteins has been reported in stroke patients. The aim of the present study was to investigate whether antibodies against N-homocysteinylated albumin are associated with coronary artery disease (CAD).We studied 88 male patients aged 50 years or under with angiographically documented CAD and 100 age-matched apparently healthy men as controls. Serum levels of IgG antibodies against Nε-Hcy-albumin were determined using an enzymelinked immunosorbent assay. Seropositivity to anti-Nε -Hcy-albumin antibodies was 5-fold more frequent in CAD patients than in controls (52.3 % vs 10.0 %; p<0.0001). Plasma Hcy levels in CAD patients were also significantly higher in the former than in the latter group (medians, 13.0 μ M vs 12.1 μ M; p=0.026). Importantly, 41.2% of subjects with plasma total Hcy >14.5 mM were seropositive compared with 25.5 % of normohomocysteinemic individuals (p=0.048).There was a weak correlation between anti-Nε-Hcy-albumin antibodies and Hcy levels (r=0.16; p=0.03). By multivariate logistic regression analysis, seropositivity to anti-Nε-Hcy-albumin antibodies was an independent predictor of early CAD (OR, 14.82; 95% CI, 4.47 to 49.19; p=0.00002). Interestingly, anti-Nε-Hcy-albumin antibodies were associated with C-reactive protein levels (r=0.24; p=0.002). Seropositivity to anti-Nε-Hcy-albumin antibodies showed no association with the MTHFR C677T polymorphism. Our results suggest that seropositivity to antibodies against Nε-homocysteinylated albumin is associated with early-onset CAD. An autoimmune response to Nε-Hcy-albumin may represent a novel mechanism involved in the early development of CAD.


Circulation ◽  
2000 ◽  
Vol 102 (11) ◽  
pp. 1227-1232 ◽  
Author(s):  
Jeffrey L. Anderson ◽  
Joseph B. Muhlestein ◽  
Benjamin D. Horne ◽  
John F. Carlquist ◽  
Tami L. Bair ◽  
...  

Gene ◽  
2015 ◽  
Vol 571 (1) ◽  
pp. 28-32 ◽  
Author(s):  
Prithiksha Ramkaran ◽  
Alisa Phulukdaree ◽  
Sajidah Khan ◽  
Devapregasan Moodley ◽  
Anil A. Chuturgoon

2010 ◽  
Vol 42 (2) ◽  
pp. 259-265 ◽  
Author(s):  
Motoyuki Iemitsu ◽  
Haruka Murakami ◽  
Kiyoshi Sanada ◽  
Kenta Yamamoto ◽  
Hiroshi Kawano ◽  
...  

The TT genotype of C677T polymorphism in 5,10-methylenetetrahydrofolate reductase (MTHFR) induces elevation of homocysteine level and leads to atherosclerosis and arterial stiffening. Furthermore, cardiorespiratory fitness level is also associated with arterial stiffness. In the present study, a cross-sectional investigation of 763 Japanese men and women (18–70 yr old) was performed to clarify the effects of cardiorespiratory fitness on the relationship between arterial stiffness and MTHFR C677T gene polymorphism. Arterial stiffness was assessed by carotid β-stiffness with ultrasonography and tonometry. The study subjects were divided into high-cardiorespiratory fitness (High-Fit) and low-cardiorespiratory fitness (Low-Fit) groups based on the median value of peak oxygen uptake in each sex and decade. The plasma homocysteine level was higher in the TT genotype of MTHFR C677T polymorphism compared with CC and CT genotype individuals. MTHFR C677T polymorphism showed no effect on carotid β-stiffness, but there was a significant interaction effect between fitness and MTHFR C677T polymorphism on carotid β-stiffness ( P = 0.0017). In the Low-Fit subjects, carotid β-stiffness was significantly higher in individuals with the TT genotype than the CC and CT genotypes. However, there were no such differences in High-Fit subjects. In addition, β-stiffness and plasma homocysteine levels were positively correlated in Low-Fit subjects with the TT genotype ( r = 0.71, P < 0.0001), but no such correlations were observed in High-Fit subjects. In CC and CT genotype individuals, there were also no such correlations in either fitness level. These results suggest that the higher cardiorespiratory fitness may attenuate central artery stiffening associated with MTHFR C677T polymorphism.


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