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

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

British Journal of Ophthalmology ◽

10.1136/bjo.85.7.803 ◽

2001 ◽

Vol 85 (7) ◽

pp. 803-806 ◽

Cited By ~ 34

Author(s):

M. Weger

Keyword(s):

Risk Factor ◽

Optic Neuropathy ◽

Mthfr C677t ◽

Ischaemic Optic Neuropathy ◽

C677t Mutation

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Hyperhomocysteinemia and C677T MTHFR Genotype in Patients With Retinal Vein Thrombosis

Clinical and Applied Thrombosis/Hemostasis ◽

10.1177/1076029609348644 ◽

2009 ◽

Vol 16 (5) ◽

pp. 549-553 ◽

Cited By ~ 21

Author(s):

Gianluca Sottilotta ◽

Simona Maria Siboni ◽

Caterina Latella ◽

Vincenzo Oriana ◽

Ermelinda Romeo ◽

...

Keyword(s):

Risk Factor ◽

Methylenetetrahydrofolate Reductase ◽

Mthfr C677t ◽

Control Group ◽

Vein Thrombosis ◽

Mthfr Genotype ◽

C677t Mthfr ◽

High Prevalence ◽

Recent Diagnosis ◽

Deep Vein

Introduction: Elevated homocysteine (Hcy) is associated with the risk of deep vein thrombosis, pulmonary embolism, ischemic heart disease, and stroke. Several studies have suggested that hyperhomocysteinemia (HHcy) may predispose to retinal vein thrombosis (RVT) development. The aim of this study is to investigate the relationship between Hcy, C677T methylenetetrahydrofolate reductase (MTHFR) genotype, and RVT in patients compared with controls. Materials and Methods: We evaluated the Hcy plasma level of 3114 consecutive participants in 2 Italian centers during a 2-year period. Hyperhomocysteinemia was found in 99 patients and 136 healthy participants. Of the 99 patients, 20 had RVT with a high prevalence of HHcy in the RVT subgroup (20.2%). This result suggested a possible relationship between HHcy and RVT development. We investigated 105 consecutive patients with recent diagnosis of RVT, and we compared them with 226 healthy controls to evaluate whether HHcy may be a risk factor for RVT. Results: the prevalence of HHcy was higher in patients compared with controls (34.3% vs 14.2%; P < .001). The MTHFR C677T genotype was found in 69 of 105 (65.7%) patients with RVT (heterozygosity: 40 of 105 and homozygosity: 29 of 105). The control group showed the presence of MTHFR C677T genotype in 169 of 226 participants (74.8%; heterozygosity: 100 of 226 and homozygosity: 69 of 226) without difference between the 2 groups (P = .08). Conclusion: our study suggests that HHcy is a possible risk factor for RVT development, while no association was found between RVT and the C677T MTHFR genotype.

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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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Knowledge, awareness and perceptions of diabetes mellitus among the Saudi population

Journal of Comparative Effectiveness Research ◽

10.2217/cer-2019-0137 ◽

2020 ◽

Vol 9 (6) ◽

pp. 413-422

Author(s):

Muhammad H Mujammami ◽

Abdulaziz A Alodhayani ◽

Mohammad Ibrahim AlJabri ◽

Ahmad Alhumaidi Alanazi ◽

Sultan Sayyaf Alanazi ◽

...

Keyword(s):

Diabetes Mellitus ◽

Risk Factors ◽

Social Media ◽

Risk Factor ◽

Healthcare Workers ◽

Health Workers ◽

Saudi Population ◽

Limited Data ◽

High Prevalence ◽

Associated Risk Factors

Background: High prevalence of undiagnosed cases of diabetes mellitus (DM) has increased over the last two decades, most patients with DM only become aware of their condition once they develop a complication. Limited data are available regarding the knowledge and awareness about DM and the associated risk factors, complications and management in Saudi society. Aim: This study aimed to assess knowledge of DM in general Saudi society and among Saudi healthcare workers. Results: Only 37.3% of the participants were aware of the current DM prevalence. Obesity was the most frequently identified risk factor for DM. Most comparisons indicated better awareness among health workers. Conclusion: A significant lack of knowledge about DM in Saudi society was identified. Social media and educational curriculum can improve knowledge and awareness of DM.

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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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The RATIONS (Reducing Activation of Tuberculosis by Improvement of Nutritional Status) study: a cluster randomised trial of nutritional support (food rations) to reduce TB incidence in household contacts of patients with microbiologically confirmed pulmonary tuberculosis in communities with a high prevalence of undernutrition, Jharkhand, India

BMJ Open ◽

10.1136/bmjopen-2020-047210 ◽

2021 ◽

Vol 11 (5) ◽

pp. e047210

Author(s):

Anurag Bhargava ◽

Madhavi Bhargava ◽

Banurekha Velayutham ◽

Kannan Thiruvengadam ◽

Basilea Watson ◽

...

Keyword(s):

Risk Factor ◽

Nutritional Status ◽

G Proteins ◽

Randomised Trial ◽

Cluster Randomised Trial ◽

Household Contacts ◽

Cluster Randomised ◽

High Prevalence ◽

Secondary Outcomes ◽

The Impact

IntroductionIndia has the largest burden of cases and deaths related to tuberculosis (TB). Undernutrition is the leading risk factor accounting for TB incidence, while severe undernutrition is a common risk factor for mortality in patients with TB in India. The impact of nutritional supplementation on TB incidence is unknown, while few underpowered studies have assessed its impact on TB mortality. We designed an open-label, field-based cluster randomised trial to assess the impact of nutritional supplementation (with food rations) on TB incidence in a group at higher risk of TB infection and disease, viz household contacts (HHC) of patients with microbiologically confirmed pulmonary TB (PTB) in Jharkhand, a state with a high prevalence of undernutrition.Methods and analysisWe shall enrol 2800 adult patients with PTB of the national TB programme, across 28 treatment units in 4 districts, and their approximately 11 200 eligible contacts. The sample size has 80% power to detect the primary outcome of 50% reduction in incidence of active TB in HHC over 2 years of follow-up. Patients and HHC in both the arms will undergo nutritional assessment and counselling. Patients will receive monthly food rations (supplying 1200 kcal and 52 g proteins/day) and multivitamins along with antitubercular treatment. The HHC in the intervention arm will receive food rations (supplying 750 kcal and 23 g proteins/day) and multivitamins while HHC in control arm will be on usual diet. The secondary outcomes in HHC will include effects on nutritional status, non-TB infections. Secondary outcomes in patients are effects on TB mortality, adherence, adverse effects, nutritional and performance status. Substudies will examine micronutrient status and effects on dietary intake, body composition, muscle strength and immune function.Ethics and disseminationThe institutional ethics committee of ICMR-NIRT, Chennai, approved the study (289/NIRT-IEC/2018). The results will be disseminated in publications and presentations.Trial registration numberClinical Trial Registry of India: CTRI/2019/08/020490.

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Healthcare associated pneumonia: An old concept at a hospital with high prevalence of antimicrobial resistance

MedPharmRes ◽

10.32895/ump.mpr.5.2.4 ◽

2021 ◽

Vol 5 (2) ◽

pp. 17-21

Author(s):

Lam Nguyen-Ho ◽

Duong Hoang-Thai ◽

Vu Le-Thuong ◽

Ngoc Tran-Van

Keyword(s):

Risk Factor ◽

Antimicrobial Resistance ◽

Multidrug Resistant ◽

Community Acquired Pneumonia ◽

Resistant Organism ◽

Healthcare Associated Infection ◽

Female Ratio ◽

High Prevalence ◽

Need To Evaluate ◽

Healthcare Associated

Background: One of several reasons that the concept of healthcare-associated pneumonia (HCAP) was dismissed was the same presence of multidrug resistant organism (MDRO) between community-acquired pneumonia and HCAP at countries with the low prevalence of antimicrobial resistance (AMR). However, this finding could be unsuitable for countries with the high rates of AMR. Methods: A prospective observational study was conducted at the respiratory department of Cho Ray hospital from September 2015 to April 2016. All adult patients suitable for community acquired pneumonia (CAP) with risk factor for healthcare-associated infection were included. Results: We found out 130 subjects. The median age was 71 years (interquartile range 57-81). The male/female ratio was 1.55:1. Prior hospitalization was the most common risk factor for healthcare-associated infection. There were 35 cases (26.9%) with culture-positive (sputum and/or bronchial lavage). Isolated bacteria included Pseudomonas aeruginosa (9 cases), Klebsiella pneumoniae (9 cases), Escherichia coli (4 cases), Acinetobacter baumannii (6 cases), and Staphylococcus aureus (7 cases) with the characteristic of AMR similar to the bacterial spectrum associated with hospital-acquired pneumonia. Conclusion: MDROs were detected frequently in CAP patients with risk factor for healthcare-associated infection at the hospital with the high prevalence of AMR. This requires the urgent need to evaluate risk factors for MDRO infection in community-onset pneumonia when the concept of HCAP is no longer used.

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