Methylenetetrahydrofolate reductase polymorphism (C677T), hyperhomocysteinemia, and risk of ischemic cardiovascular disease and venous thromboembolism: prospective and case-control studies from the Copenhagen City Heart Study (original) (raw)
Related papers
Pteridines, 2010
The aim of the present study was to explore the influence of age and gender, on the association between the methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism and plasma total homocysteine (tHcy) concentrations in patients with cardiovascular disease (CVD). Fasting tHcy and the MTHFR C677T mutation were evaluated in 98 patients with CVD, 46 were men and 52 women (aged 20-96 years). There was a significant elevation of plasma tHcy with age (<45 yr: 33.9 µmol/L vs. >75 yr: 43.6 µmol/L; p <0.01). The mean tHcy concentration increased significantly with age in men (<55 yr: 33.4 µmol/L vs. >55yr: 42.45 µmol/L; p 0.01). However, the plasma tHcy was not increased with older age in women. The frequency of the TT genotype was 19.6% in the younger patients group (>55 yr) compared with 4.7% in the older patients group (>55 yr; p <0.01). In conclusion, the data presented here are consistent with genetic factors that influence tHcy levels being more prominent in old patients (>55 yr). Then, the MTHFR mutation does not seem to be associated with either high tHcy or the occurrence of CVD.
Clinical and Applied Thrombosis/Hemostasis, 2012
There is limited data on the role of hyperhomocysteinemia as a risk factor for cerebral veno-sinus thrombosis (CVT) in Indians. We examined the association between plasma homocysteine (Hcy), methylenetetrahydrofolate reductase ( MTHFR) C677T polymorphism, and CVT in 185 patients with aseptic CVT (puerperal 80 and nonpuerperal 105) and 248 healthy controls (puerperal 67 and nonpuerperal 181). Fasting Hcy was higher in patients compared to controls (20.25 ± 5.97 vs 9.81 ± 5.19 μmol/L, P < .001) and associated with 4.54-fold (95% confidence interval [CI]: 2.74-7.53) increase in risk of CVT. Risk was higher in puerperal (odds ratio [OR]: 8.7, 95% CI: 2.73-26.91) compared to nonpuerperal CVT (OR: 3.82, 95% CI: 2.09-6.96). Plasma Hcy was higher in MTHFR 677TT compared to 677CT and 677CC genotypes (34.44 ± 32.8 vs 25.81 ± 33.3 vs 18.50 ± 23.7 μmol/L, respectively, P < .001), but the risk associated with MTHFR 677TT was insignificant (OR: 1.91, 95% CI: 0.53-7.06). We conclude that hyp...
Vascular specialist international, 2015
Deep venous thrombosis (DVT) is a common but elusive condition characterized by a high morbidity and mortality rate. The aim of the present study was to investigate the correlation between methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism with plasma total homocysteine (tHcy) levels and DVT risk in an Iranian population. Materials and Methods: Our study population consisted of 67 patients with a diagnosis of DVT and 67 healthy subjects as controls. Genotyping of MTHFR C677T polymorphism was performed by the polymerase chain reaction technique combined with restriction enzyme fragment length polymorphism (PCR-RFLP) and measurement of tHcy levels was done by enzyme immunoassay method. Results: Plasma tHcy levels were significantly higher in DVT patients than controls (18.09±7.6 vs. 10.5±4.3, P=0.001). Also, plasma tHcy levels were significantly higher in MTHFR 677TT genotypes compared to 677CC genotypes in both DVT patients (P=0.016) and controls (P=0.03). Neither heterozygote nor homozygote genotypes of MTHFR C677T polymorphism was significantly correlated with DVT (P>0.05). The distribution of MTHFR C677T genotypes was similar between men and women in both DVT patients and controls (P>0.05). Moreover, the frequency of mutant 677T allele did not differ significantly between the two groups (28.3% vs. 21.6%, P=0.15). Conclusion: Based on this study, we propose that hyperhomocysteinemia but not homozygosity for MTHFR C677T polymorphism is a significant risk factor for DVT in the Iranian population. Also, MTHFR 677TT genotype is a determinant of elevated plasma tHcy levels.
Circulation, 1998
Background-The results of retrospective and prospective case-control studies have clearly established that mild elevations of the plasma homocysteine level are associated with increased risk of coronary, cerebral, and peripheral vascular disease. Recently, a mutation (677C3 T) was identified in the methylenetetrahydrofolate reductase (MTHFR) gene that results in reduced folate-dependent enzyme activity and reduced remethylation of homocysteine to methionine. Mutant homozygotes (TT genotype) constitute Ϸ12% of the white population and frequently have mildly elevated circulating homocysteine. Therefore, it seems likely that they would also be at increased risk of vascular disease. A number of studies have investigated this during the past 3 years, and the present article evaluates the results in a meta-analysis. Methods and Results-We identified 13 studies in which there were measurements of plasma homocysteine in relation to the 3 genotypes (TT, CT, and CC) and 23 case-control studies comprising 5869 genotyped cardiovascular disease patients (mostly coronary artery disease) and 6644 genotyped control subjects. Those bearing the TT genotype had plasma homocysteine concentrations 2.6 mol/L (25%) higher than those with the CC genotype. However, there was no difference between patients and control subjects either in the frequency of mutant alleles (T) (34.3% versus 33.8%) or the TT genotype (11.9% versus 11.7%). In the analysis of the 23 studies, the relative risk (OR) of vascular disease associated with the TT genotype was 1.12 (95% CI, 0.92 to 1.37). Conclusions-We conclude that although the C677T/MTHFR mutation is a major cause of mild hyperhomocysteinemia, the mutation does not increase cardiovascular risk. Our findings suggest that the mild hyperhomocysteinemia found frequently in vascular disease patients is not causally related to the pathogenesis of the vascular disease. (Circulation.
The graded effect of hyperhomocysteinemia on the severity and extent of coronary atherosclerosis
Atherosclerosis, 1999
It is not clear to what extent methylenetetrahydrofolate reductase (MTHFR) gene and hyperhomocysteinemia effect the severity and extent of coronary atherosclerosis in Asian populations. We examined the MTHFR genotypes and plasma homocysteine (HCY) concentrations in 192 Taiwanese and investigated their relationship with coronary artery disease (CAD), and the severity and extent of coronary atherosclerosis. The distribution of MTHFR genotypes was similar in 116 CAD patients and 76 non-CAD subjects. Homozygosity was noted in 8% of CAD patients and 13% of non-CAD subjects (P = 0.33; 95% CI, 0.2 -1.6). The geometric mean of HCY values was higher in CAD patients (11.10 91.51 mmol/l) than in non-CAD subjects (9.21 91.55 mmol/l) (P= 0.003). HCY levels were higher in patients with multi-vessel disease (P B 0.05) or in patients with ]90% stenotic lesions (P=0.005), compared with non-CAD subjects. The CAD risks in the top two HCY quartiles ( ] 14.0 and 10.1 -13.9 mmol/l) were 4.0 (95% CI, 1.7-9.2) and 3.2 (95% CI, 1.4-7.4) times higher than in the lowest quartile (5 7.9 mmol/l) (P = 0.001 and 0.007, respectively). Linear regression analysis showed significant correlations between HCY concentrations and the severity and extent of atherosclerosis (P=0.0001 for both). In conclusion, hyperhomocysteinemia appears to have a graded effect on the risk of CAD as well as the severity and extent of coronary atherosclerosis. Our findings do not support the homozygous genotype of MTHFR as a genetic risk factor for CAD in this Taiwanese population. Perhaps a further study including assessment of vitamin status is needed to better clarify the relationship between MTHFR genotypes and CAD. : S 0 0 2 1 -9 1 5 0 ( 9 9 ) 0 0 2 0 8 -7
Acta biochimica Polonica, 2008
DVT. Plasma concentration of tHcy was significantly increased in AA genotype of patients with OAD, but not in patients with DVT. We found a significant increase of plasma tHcy in patients with OAD in comparison with healthy respondents for normal:heterozygote (CC:AC), heterozygote:normal (CT:AA), and heterozygote:heterozygote (CT:AC) haplotypes. Plasma concentration of tHcy in patients with DVT in comparison with healthy respondents was significantly increased for normal:normal (CC:AA), normal heterozygote (CC:AC), and heterozygote:heterozygote (CT:AC) haplotypes. We conclude that MTHFR C677T and MTHFR A1289C genotypes and haplotypes are connected with tHcy plasma levels in Macedonian patients with OAD and DVT.
Journal of Pediatric Hematology/Oncology, 2011
There are limited data regarding the role of methylene tetrahydrofolate reductase (MTHFR) A1298C polymorphism and hyperhomocysteinemia as risk factors for retinal vein thrombosis (RVT) in Iranians. This study aimed to examine a possible association between fasting plasma total homocysteine (tHcy) levels, MTHFR A1298C polymorphism and RVT development in Iranian patients. Our study population consisted of 73 patients with a diagnosis of RVT (52.7 W 16.2 years) and 73 age and sex-matched healthy controls (49.1 W 14.6 years). Genotyping for the MTHFR A1298Cpolymorphism was conducted by PCR-RFLP technique and plasma tHcy levels were measured by an enzyme immunoassay method. Fasting plasma tHcy levels were 20.29 W 8.5 mmol/l in RVT patients and 10.9 W 3.1 mmol/l in control subjects. The number of cases with abnormal tHcy values (hyperhomocysteinemia) was significantly higher in the RVT patients than control subjects (P U 0.0001). The prevalence of MTHFR 1298CC homozygote genotype was similar in RVT patients and controls (17.8 vs.15.1%, P U 0.45). There were no significant differences in genotype distribution of MTHFR A1298C polymorphism between males and females in both RVT patients and controls (P > 0.05). The frequency of the 1298C allele was 39.1 and 35.6% in patients and controls, respectively, and did not differ significantly between them (P U 0.23). Moreover, heterozygote and homozygote genotypes in the RVT patients had significantly higher abnormal tHcy values than corresponding genotypes in control subjects (P < 0.001). Our study demonstrated that hyperhomocysteinemia but not homozygosity for MTHFR A1298C polymorphism is a significant risk factor for RVT in the Iranian population. Blood Coagul Fibrinolysis 27:000-000
Journal of Medical Biochemistry, 2000
Kratak sadr`aj: Hiperhomocisteinemija se smatra nezavisnim faktorom rizika za preuranjeni razvoj kardiovaskularnih bolesti. Mutacija MTHFR C677T sni`ava aktivnost metilentetrahidro fol atreduktaze i mo`e dovesti do hiperhomocisteinemije. Inci den ca hiperhomocisteinemije (homocisteinemija iz nad 12 μmol/L), nivo homocisteina i raspodela MTHFR 677 geno ti pova (C/C,C/T,T/T) upore|eni su izme|u mladih bo les nika sa aku tnim infarktom miokarda i zdravih osoba iste dobi. Studija je obuhvatila 86 bolesnika mla|ih od 45 godina (77 mu{karaca i 9 `ena) i kontrolnu grupu od 35 osoba. Ho mocistein je od re|ivan metodom HPLC, a MTHFR 677 ge no tip PCR am pli fi ka cijom i digestijom sa Hinf I. Podaci su statisti~ki obra|eni po mo -}u Chi-square i Mann-Whitney U testa. Hiper homo ciste i ne mija je bila prisutna kod 32,6% bolesnika i 14,3% zdravih oso ba, {to pred stavlja statisti~ki zna~ajnu razliku (P=0,038). Medijane homo ci steinemija bolesnika (10,4 μmol/L) i zdravih osoba (9,6 μmol/L) bile su statisti~ki zna ~aj no razli~ite (P= 0,035). Raspodela MTHFR 677 genotipova kod bolesnika (50,0% C/C, 41,9% C/T i 8,1% T/T) nije se sta tisti~ki zna ~aj no razlikovala od raspodele u kontrolnoj gru pi. Genotip MTHFR 677 nije uti cao na incidencu hiperhomocisteinemije i nivo ho mo cisteina kod bolesnika. Mo`e se za klju ~iti da mladi bolesnici sa akutnim infarktom miokarda ima ju vi{u incidencu hiperhomo cisteinemije i vi{i nivo homo cisteina nego zdrave oso be iste starosti, prĩ emu nema zna ~ajne razlike u raspodeli geno tipova MTHFR.