Hyperhomocyst(e)inaemia, but not MTHFR C677T mutation, as a risk factor for non-arteritic ischaemic optic neuropathy

Abstract Moderate elevation of plasma total homocysteine (tHcy) is a strong and independent risk factor for coronary artery disease (CAD). It can result from genetic or nutrient-related disturbances in the transsulfuration or remethylation pathways for Hcy metabolism. A point mutation (C677T; Ala-to-Val) in the gene encoding the 5,10-methylenetetrahydrofolate reductase (MTHFR) has been recently reported to render the enzyme thermolabile and less active. Studies on the role of this mutation as a risk factor for CAD have given conflicting results. We studied a total of 415 subjects, 278 with angiographically documented multivessel CAD and 137 with angiographically documented normal coronary arteries. The overall frequency of the MTHFR V/V homozygous genotype was 15.7% (with 52.5% heterozygous and 31.8% normal). Subgroup analysis showed no significant differences between CAD and CAD-free subjects. A genotype/phenotype correlation study showed a marked effect of folate on the association between MTHFR genotypes and tHcy. Among individuals with folate levels below the median (11.5 nmol/L), fasting tHcy was significantly increased not only in V/V homozygotes (by 59%) but also, at intermediate values, in A/V heterozygotes (by 21% on average). Conversely, the mutation resulted neutral with respect to tHcy levels in subjects with adequate folate levels. We conclude that, in our population, the MTHFR C677T mutation is rather common, but it does not appear to be associated per se to CAD. A genetic-environmental interaction may contribute to the vascular risk by elevating tHcy when folate status is low.

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Methylenetetrahydrofolate Reductase C677T Mutation, Plasma Homocysteine, and Folate in Subjects From Northern Italy With or Without Angiographically Documented Severe Coronary Atherosclerotic Disease: Evidence for an Important Genetic-Environmental Interaction

Blood ◽

10.1182/blood.v91.11.4158.411k23_4158_4163 ◽

1998 ◽

Vol 91 (11) ◽

pp. 4158-4163 ◽

Cited By ~ 4

Author(s):

Domenico Girelli ◽

Simonetta Friso ◽

Elisabetta Trabetti ◽

Oliviero Olivieri ◽

Carla Russo ◽

...

Keyword(s):

Risk Factor ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Correlation Study ◽

Gene Encoding ◽

Environmental Interaction ◽

Homozygous Genotype ◽

C677t Mutation ◽

Total Homocysteine ◽

Artery Disease

Moderate elevation of plasma total homocysteine (tHcy) is a strong and independent risk factor for coronary artery disease (CAD). It can result from genetic or nutrient-related disturbances in the transsulfuration or remethylation pathways for Hcy metabolism. A point mutation (C677T; Ala-to-Val) in the gene encoding the 5,10-methylenetetrahydrofolate reductase (MTHFR) has been recently reported to render the enzyme thermolabile and less active. Studies on the role of this mutation as a risk factor for CAD have given conflicting results. We studied a total of 415 subjects, 278 with angiographically documented multivessel CAD and 137 with angiographically documented normal coronary arteries. The overall frequency of the MTHFR V/V homozygous genotype was 15.7% (with 52.5% heterozygous and 31.8% normal). Subgroup analysis showed no significant differences between CAD and CAD-free subjects. A genotype/phenotype correlation study showed a marked effect of folate on the association between MTHFR genotypes and tHcy. Among individuals with folate levels below the median (11.5 nmol/L), fasting tHcy was significantly increased not only in V/V homozygotes (by 59%) but also, at intermediate values, in A/V heterozygotes (by 21% on average). Conversely, the mutation resulted neutral with respect to tHcy levels in subjects with adequate folate levels. We conclude that, in our population, the MTHFR C677T mutation is rather common, but it does not appear to be associated per se to CAD. A genetic-environmental interaction may contribute to the vascular risk by elevating tHcy when folate status is low.

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The MTHFR C677T mutation is not a risk factor recognized for HBV-related HCC in a population with a high prevalence of this genetic marker

Infection Genetics and Evolution ◽

10.1016/j.meegid.2017.01.008 ◽

2017 ◽

Vol 49 ◽

pp. 66-72 ◽

Cited By ~ 2

Author(s):

Xiaolei Jiao ◽

Ying Luo ◽

Bin Yang ◽

Li Jing ◽

Yayue Li ◽

...

Keyword(s):

Risk Factor ◽

Genetic Marker ◽

Mthfr C677t ◽

High Prevalence ◽

C677t Mutation

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Non-Arteritic Anterior Ischaemic Optic Neuropathy: Treatment and Risk Factors

Czech and Slovak Ophthalmology ◽

10.31348/2020/15 ◽

2020 ◽

Vol 76 (2) ◽

pp. 78-87

Author(s):

Silvie Kalábová ◽

Klára Marešová ◽

Marta Karhanová

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Visual Acuity ◽

Risk Factor ◽

Optic Neuropathy ◽

Systemic Risk ◽

Systemic Disease ◽

Department Of Ophthalmology ◽

Ischaemic Optic Neuropathy ◽

Anterior Ischaemic Optic Neuropathy

Aim: To ascertain whether various therapeutic procedures in non-arteritic anterior ischaemic optic neuropathy (NAION) have an impact on the resulting visual acuity of the affected eye. To assess the prevalence of risk factors that accompany this disease according to the literature. Methods: The retrospective study enrolled 55 eyes of 53 patients (41 men, 12 women) with an age range of 46 to 85 years (mean 64.9; median 64.0) who were hospitalized at the Department of Ophthalmology of the Faculty of Medicine and Dentistry and the University Hospital in Olomouc with the diagnosis of NAION between 2005 and 2016, and who received systemic treatment with intravenous vasodilators, either alone or in combination with intravenous corticosteroids. Central visual acuity (CVA) prior to treatment and immediately after its termination was evaluated. CVA was measured using the Snellen chart and is presented in decimal values. Using medical history data and medical records, the presence of systemic disease, namely hypertension, type 2 diabetes mellitus, and hypercholesterolaemia, was studied in these patients and evaluated for a possible association with NAION. Results: In the group of patients who were treated with intravenous vasodilators, the resulting CVA improved by 0.083 on average. In the group of patients who, in addition to vasodilator therapy, also received treatment with corticosteroids, the resulting CVA improved by only 0.03 on average. Although there was a more prominent improvement in CVA in the group treated with intravenous vasodilators alone, this difference was not statistically significant. At least one risk factor was found in the vast majority of the patients (96%). Eighty percent of the patients had hypertension, 43.6% of them were treated for diabetes mellitus, and 72.7% of the patients took drugs for hypercholesterolaemia. A combination of all these conditions was found in 36.4% of the patients. The proportion of smokers and past smokers did not exceed that of non-smokers. Conclusion: The mean improvement in the resulting CVA in patients after systemic therapy with vasodilators alone was greater than in those treated with a combination of vasodilators and corticosteroids; however, this difference was not statistically significant. In most patients in the group, at least one systemic risk factor was noted, most frequently hypertension. The prevalence rate of systemic risk factors was comparable to that reported in the literature.

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Is Homozygosity for the MTHFR C677T Mutation a Risk Factor for Miscarriage? — Likely.

Blood ◽

10.1182/blood.v108.11.4079.4079 ◽

2006 ◽

Vol 108 (11) ◽

pp. 4079-4079

Author(s):

Ivy Altomare ◽

Louis M. Aledort

Keyword(s):

Systematic Review ◽

Risk Factor ◽

Pregnancy Loss ◽

Meta Analysis ◽

Fetal Loss ◽

Mthfr C677t ◽

Early Pregnancy Loss ◽

C677t Mutation ◽

Recurrent Early Pregnancy Loss ◽

In Pregnancy

Abstract Various hereditary thrombophilias such as activated protein C resistance, the factor V leiden mutation, the prothrombin G20210A mutation, protein S deficiency, hyperhomocysteinemia, or combinations of the above disorders have been linked to pregnancy loss at varying stages of gestation (Robertson L, et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol2006;132(2):171–96; Seligsohn U, et al. Genetic susceptibility to venous thrombosis. N Engl J Med2001;344(16):1222–31). The literature regarding methylenetetrahydrofolate reductase (MTHFR) mutations is confusing. Much of the evidence supporting a causal relationship between MTHFR mutations and early fetal loss comes from individual case reports with little outcome data. Three recent meta-analyses of thrombophilia in pregnancy concluded that although there may be a trend toward higher risk, the relationship between MTHFR mutations and spontaneous abortions is not truly significant (Robertson L, et al. Thrombophilia in pregnancy: a systematic review. Br J Haematol2006;132(2):171–96; Nelen WL, et al. Hyperhomocysteinemia and recurrent early pregnancy loss: a meta-analysis. Fertil Steril2000;74(6):1196–9; Rey E, et al. Thrombophilic disorders and fetal loss: a meta-analysis. Lancet2003;361(9361):901–8). In contrast, a study supporting the role of MTHFR mutations in recurrent unexplained abortions found a 2–3 fold increased risk of early fetal loss among Caucasian females homozygous for the C677T mutation versus normal controls (Nelen WL, et al. Genetic risk factor for unexplained recurrent early pregnancy loss. Lancet1997;350(9081):861). We present 5 patients with this genetic defect who presented consecutively to our clinic for decision making for future pregnancies. Each had strong histories of miscarriages after the 8th week of gestation. The clinical features of these patients are reported in the table below. Each woman is Caucasian, and is homozygous for the MTHFR C677T mutation with no other acquired or hereditary thrombophilias. Homocysteine levels were also in normal range for each patient. Our case series of 5 Caucasian women gives support to the theory of a causal relationship between MTHFR mutations and fetal loss. We recommended anticoagulation with low-molecular weight or unfractionated heparin for each patient as a therapeutic intervention to reduce the risk of recurrent abortion in future pregnancies.

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Methylenetetrahydrofolate reductase polymorphisms as risk factors for retinal venous occlusive disease: A literature review

European Journal of Ophthalmology ◽

10.1177/11206721211000647 ◽

2021 ◽

pp. 112067212110006

Author(s):

Manuel Marques ◽

Francisco Alves ◽

Miguel Leitão ◽

Catarina Rodrigues ◽

Joana Tavares Ferreira

Keyword(s):

Risk Factors ◽

Literature Review ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Mthfr Gene ◽

Mthfr Polymorphisms ◽

Vein Occlusion ◽

C677t Mutation ◽

Retinal Vascular Disease

The role of polymorphisms of methylenetetrahydrofolate reductase (MTHFR) gene in retinal vein occlusion (RVO) is a theme of discussion since the first reports of RVO in patients with MTHFR C677T mutation and without classic acquired risk factors for retinal vascular disease. The association between MTHFR polymorphisms and RVO has been studied over the last 20 years producing conflicting results. This review aims to summarize the literature concerning the role MTHFR polymorphisms as risk factors for RVO.

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