Hyperhomocysteinaemia: a metabolic risk factor for coronary heart disease determined by both genetic and environmental influences?

Daly, Leslie; Robinson, Killian; Tan, Kaixuan; Graham, Ian

doi:10.1093/qjmed/86.10.685

Cited by 42 publications

(12 citation statements)

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“…However, the frequency of heterozygosity for CBS and MTHFR deficiency is too low to account for the frequency of mildly elevated homocysteine levels in patients with cardiovascular disease. 13 MTHFR is a flavoprotein that reduces 5,10-methylenetetrahydrofolate to 5-methyltetrahydrofolate, the predominant circulating form of folate. In 1988, Kang et al5 described a new MTHFR variant with thermolabile properties.…”

Section: Methods and Resultsmentioning

confidence: 99%

Thermolabile Methylenetetrahydrofolate Reductase in Coronary Artery Disease

Kluijtmans¹,

Kastelein²,

Lindemans³

et al. 1997

Circulation

196

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Background Hyperhomocysteinemia, an independent and graded risk factor for coronary artery disease (CAD), may result from both environmental and hereditary factors. Methylenetetrahydrofolate reductase (MTHFR) catalyzes the conversion of methylenetetrahydrofolate to methyltetrahydrofolate, the methyl donor in the remethylation of homocysteine to methionine. A 677C→T mutation in the MTHFR gene has been associated with elevated homocysteine concentrations in homozygous (+/+) individuals. Methods and Results We assessed the frequency of this common mutation in 735 CAD patients from the Regression Growth Evaluation Statin Study (REGRESS), a lipid-lowering coronary-regression trial, and in 1250 population-based control subjects. Furthermore, the association between the mutation and serum homocysteine concentrations was studied. The frequency of the homozygous (+/+) mutation was 9.5% among patients versus 8.5% among control subjects, resulting in an odds ratio of 1.21 (95% confidence interval [CI], 0.87 to 1.68), relative to the (−/−) genotype. Homocysteine concentrations were significantly elevated in both (+/+) and (+/−) individuals compared with (−/−) individuals (median homocysteine levels, 15.4, 13.4, and 12.6 μmol/L, for (+/+), (+/−), and (−/−) individuals, respectively). For a summary estimation of the risk of the (+/+) genotype for CAD, we performed a meta-analysis on 8 different case-control studies on thermolabile MTHFR in CAD. In the meta-analysis, the homozygous (+/+) genotype was present in 299 of 2476 patients (12.1%) and in 257 (10.4%) of 2481 control subjects, resulting in a significant odds ratio of 1.22 (95% CI, 1.01 to 1.47) relative to the (−/−) genotype. Conclusions Both the homozygous (+/+) and heterozygous (+/−) genotype result in elevated homocysteine concentrations. From our meta-analysis, we conclude that the homozygous (+/+) genotype is a modest but significant risk factor for CAD.

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Section: Methods and Resultsmentioning

confidence: 99%

Thermolabile Methylenetetrahydrofolate Reductase in Coronary Artery Disease

Kluijtmans¹,

Kastelein²,

Lindemans³

et al. 1997

Circulation

196

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“…In a previous study, we an incidence of a thermolabile MTHFR o r in a large group of obligate erozygotes for CS-deficiency studied by question naires [28]. Furthermore, even in populations with the highest prevalence of homozygous CS-defi ciency, such as in Ireland, the calculated number of carriers is too low to account for the number of observed hyperhomocysteinemic vascular patients [29]. Indeed, very recently, it was reported that the finding of lowered CS-activity was not repro ducible in 96% of studied hyperhomocysteinemic to produce a MTHFR patients and lively [30], [13,14].…”

Section: Vascular Complications In Family Membersmentioning

confidence: 99%

Prevalence of familial mild hyperhomocysteinemia

et al. 1996

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Previous studies have shown that elevated basal homocysteine levels are correlated among family members of patients with coronary vascular disease and juvenile venous thrombosis. This suggests the possibility of the presence of inherited basal mild hyperhomocysteinemia (mHH). We studied homocysteine levels, fasting as well as after methionine load, among 96 family members of 21 post-load hyperhomocysteinemic vascular index patients, i.e. 6 parents, 27 offspring, 38 siblings, 19 uncles and aunts and 6 cousins. In 15 out of 21 screened families post-load ml-IH was esti in at least one family member. Fa:>ting and post-load mHH was observed in 19 out of 89 (21%) screened family members (fasting homocysteine levels not measured in seven family members), and 31 out of 96 screened family members (32%), respectively. In 40% of all family members, post-load mHH was not accompanied by fasting mHH.conclude that both fasting and post-load mHH seems to be inherited in the majority of ic vascular patients.

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“…[1][2][3][4] Plasma homocysteine concentrations are influenced by many envinromental (folate, vitamin B6 and vitamin B12 intake) and genetic factors. [5][6][7] Deficiencies in vitamins B6, B12 and folate, which are essential coenzymes in homocysteine metabolism, elevate plasma homocysteine levels (tHcy). 8,9 The methylation of homocysteine to methionine is catalysed by the 5,10-methylenetetrahydrofolate reductase (MTHFR) enzyme (E.C.…”

Section: Introductionmentioning

confidence: 99%

C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease

Yılmaz

İşbir

Ağaçhan

et al. 2005

Cell Biochem. Funct.

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Elevated levels of homocysteine is a risk factor for coronary artery disease. The C677T transition in methylenetetrahydrofolate reductase (MTHFR) is associated with increased homocysteine levels in the general population. We analysed the association between the MTHFR C677T polymorphism and serum homocysteine concentrations in patients with coronary artery disease (CAD). Allele frequencies for the 'C' (wild-type) and 'T' alleles were 0.71 and 0.29 in CAD patients and 0.70 and 0.30 in controls, respectively. There was no difference in the distribution of MTHFR genotypes between patients with CAD and control subjects (p > 0.05). In the patient group, homocysteine levels were higher than controls but not significantly (13.99 +/- 7.44 vs. 11.77 +/- 5.18 micromol l(-1); p > 0.05). Serum homocysteine concentration was significantly higher in the TT genotype with respect to CC and CT genotypes in both the control group (p < 0.01) and patient group (p < 0.01). Systolic and diastolic blood pressures in subjects with different MTHFR genotypes did not differ significantly. In conclusion, MTHFR C677T mutation was significantly related to hyperhomocysteinemia. In spite of the clear effect of the MTHFR polymorphism on elevated homocysteine levels, we did not observe any associations among the MTHFR genotypes with a the risk of CAD in the Turkish population.

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Hyperhomocysteinaemia: a metabolic risk factor for coronary heart disease determined by both genetic and environmental influences?

Cited by 42 publications

References 0 publications

Thermolabile Methylenetetrahydrofolate Reductase in Coronary Artery Disease

Thermolabile Methylenetetrahydrofolate Reductase in Coronary Artery Disease

Prevalence of familial mild hyperhomocysteinemia

C677T mutation of methylenetetrahydrofolate reductase gene and serum homocysteine levels in Turkish patients with coronary artery disease

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