Prevalence Of Methylenetetrahydrofolate Reductase Research Articles

Deep venous thrombosis and thrombophilic mutations in western Iran: association with factor V Leiden

The aim of present study was to investigate the prevalence of factor V Leiden (FVL) c.1691G>A, prothrombin g.20210G>A and methylenetetrahydrofolate reductase (MTHFR) c.677C>T in deep vein thrombosis (DVT) patients and their possible association with DVT in western Iran. Eighty DVT patients with the mean age of 42.07 +/- 13.0 years including 44 women and 36 men and 100 sex-matched healthy individuals with the mean age of 37.63 +/- 13.3 years from Kermanshah Province of Iran with ethnic background of Kurd were studied for FVL c.1691G>A, prothrombin g.20210G>A and MTHFR c.677C>T by PCR-restriction fragment length polymorphism (RFLP) method using MnlI, HindIII and HinfI restriction enzymes, respectively. Prevalence of FVL was 11.4% in patients and 2% in control group. A significant association was found between FVL mutation and DVT with odds ratio (OR) of 6.3 [95% confidence interval (CI) = 1.32-30.05; P = 0.012]. The prevalence of prothrombin g.20210G>A variant in patients (3.8%) was nonsignificantly higher than control individuals (1.0%; OR 3.8; 95% CI = 0.39-37.81; P = 0.32). The prevalence of MTHFR c.677C>T in patients was 38.7% that was not statistically different from control group (44% P = 0.12). Venous thrombosis in legs was the most frequent clinical manifestation (n = 75), corresponding to 93.8% of the thromboembolism, followed by pulmonary thromboembolism (6.2%). We have, for the first time, determined the prevalence of inherited thrombophilia in a homogenous ethnic group of DVT patients and shown that FVL may be a risk factor for DVT in western Iran.

The Prevalence of Methylenetetrahydrofolate Reductase 677 C-T, Factor V 1691 G-A, and Prothrombin 20210 G-A Mutations in Healthy Populations in Sétif, Algeria

The polymorphic mutation 677 C-T in the methylenetetrahydrofolate reductase (MTHFR) gene presents a heterogeneous worldwide distribution and is associated with different disorders such as cardiovascular disease. Its frequency shows great ethnic and geographic variations. The aim of this work is to determine the frequency of MTHFR 677 C-T and coexistence of MTHFR 677 C-T with 2 other common, hereditary thrombophilia causes-namely, factor V 1691 G-A and prothrombin (PT) 20210 G-A mutation-in the Sétif region of Algeria. The study involved 147 apparently healthy participants (82 men and 65 women). Genotyping was carried out by a real-time polymerase chain reaction. The MTHFR 677T carrier frequency was found to be 54.4% (80/147); 59 individuals were heterozygous (40.1%), and 21 were homozygous (14.3%). The frequency of MTHFR 677T was found to be 34.3%. Among the 147 individuals, 3 (2.0%) had factor V Leiden, and 5 (3.4%) had PT 20210 A mutation. Of the 80 participants with MTHFR 677T mutation, 2 had heterozygote factor V 1691 G-A gene mutation, and 4 had heterozygote PT 20210 G-A gene mutation. The results showed that MTHFR 677T prevalence is quite high: an allelic frequency of 34.3% with a genotype frequency of 14.3%. Factor V 1691 G-A and PT 20210 G-A gene mutations are rare in the healthy population of the Sétif region of Algeria.

The 19-bp deletion of dihydrofolate reductase (DHFR), methylenetetrahydrofolate reductase (MTHFR) C677T, Factor V Leiden, prothrombin G20210A polymorphisms in cancer patients with and without thrombosis

Venous thromboembolism (VTE) is a common complication in cancer patients. Several genetic risk factors related to thrombophilia are known; however, their contributions to thrombotic tendency in cancer patients have conflicting results. In the present study, we have focused on the prevalence of methylenetetrahydrofolate reductase (MTHFR) C677T, dihydrofolate reductase (DHFR) 19-bp deletion within intron 1, factor V Leiden (FVL), and prothrombin (PT) G20210A polymorphisms in cancer patients with and without VTE. The study consisted of 63 cancer patients with VTE (group 1) and 124 cancer patients who had no evidence of VTE (group 2). Four gene polymorphisms were determined by the method of polymerase-chain-reaction-based DNA analysis. The prevalence of DHFR 19-bp deletion and MTHFR C677T polymorphisms was similar in two groups (p > 0.05). The frequency of FVL was significantly higher in group1 compared with group 2 (31.7% vs. 1.6%, p < 0.0001), but PT G20210A polymorphism was not associated with VTE. Cancer patients with thrombosis should be evaluated for FVL, but routine screening for PT G20210A, MTHFR C677T and DHFR 19-bp deletion polymorphisms is not suggested.

The Association Between Common C677T Mutation in Methylenetetrahydrofolate Reductase Gene and the Risk of Venous Thrombosis in an Iranian Population

Background: Venous thrombosis is a multicausal disease involving acquired and genetic factors. The prevalence of methylenetetrahydrofolate reductase (MTHFR) C677T genotypes and its association with venous thrombosis is not established in the Iranian population. In this study we investigated a possible association between fasting hyperhomocysteinemia and C677T mutation in the MTHFR gene with venous thrombosis. Materials and Methods: We studied 200 venous thrombotic patients and 100 healthy controls, of similar age and sex. Mutation analysis was carried out by PCR-RFLP, and the homocysteine level was measured by EIA. Results: No significant differences in the frequency of C677T genotypes were observed between patients and controls (P=0.2). The frequency of the T allele was 21% and 27.2% in controls and patients, respectively (odds ratio, 1.27; 95% CI, 0.83–1.94, P=0.15). Fasting homocysteine level was significantly higher in patients than controls (P=0.001). Conclusions: We concluded that hyperhomocysteinemia, but not MTHFR C677T mutation, is a significant risk factor for venous thrombosis in the Iranian population, and measuring the level of homocysteine is less expensive and more useful than the genetic test for the MTHFR mutation.

Hyperhomocysteinemia and prevalence of polymorphisms of homocysteine metabolism-related enzymes in patients with inflammatory bowel disease

OBJECTIVES: Patients with inflammatory bowel disease (IBD) have an increased risk of thrombotic complications. Moreover, a hypercoagulable state has been hypothesized as a contributing factor in the pathogenesis of IBD. Recently, a growing amount of interest has focused on mild-to-moderate hyperhomocysteinemia as a risk factor for thromboembolic disease. We aimed to evaluate the prevalence of hyperhomocysteinemia in patients with IBD and to investigate the contribution of genetic defects in the enzymes involved in homocysteine (Hcy) metabolism and vitamin status in determining increased levels of plasma total Hcy (tHcy). METHODS: The concentrations of tHcy, folate, and vitamin B 12 as well as the prevalence of methylenetetrahydrofolate reductase (MTHFR) 677C to T mutation and the 68-bp insertion at exon 8 of cystathionine β-synthase (CBS) were measured in patients with IBD and healthy controls. Results: In all, 17 out of 64 IBD patients (26.5%) and four out of 121 (3.3%) controls had hyperhomocysteinemia with a statistically significant difference ( p < 0.0001. No significant difference was found between IBD patients and controls with regard to the prevalence of homozygotes for the C677T variant (TT) of MTHFR or the prevalence of heterozygotes for the CBS-gene mutation (IN). Among the IBD patients the only independent factor significantly associated with hyperhomocysteinemia was folate deficiency ( p = 0.0002), regardless of the MTHFR or the CBS genotype. CONCLUSIONS: IBD patients have a higher prevalence of hyperhomocysteinemia than do healthy controls. Folate deficiency is the only independent risk factor in developing hyperhomocysteinemia.

Hyperhomocysteinemia and prevalence of polymorphisms of homocysteine metabolism-related enzymes in patients with inflammatory bowel disease.

Patients with inflammatory bowel disease (IBD) have an increased risk of thrombotic complications. Moreover, a hypercoagulable state has been hypothesized as a contributing factor in the pathogenesis of IBD. Recently, a growing amount of interest has focused on mild-to-moderate hyperhomocysteinemia as a risk factor for thromboembolic disease. We aimed to evaluate the prevalence of hyperhomocysteinemia in patients with IBD and to investigate the contribution of genetic defects in the enzymes involved in homocysteine (Hcy) metabolism and vitamin status in determining increased levels of plasma total Hcy (tHcy). The concentrations of tHcy, folate, and vitamin B12 as well as the prevalence of methylenetetrahydrofolate reductase (MTHFR) 677C to T mutation and the 68-bp insertion at exon 8 of cystathionine beta-synthase (CBS) were measured in patients with IBD and healthy controls. In all, 17 out of 64 IBD patients (26.5%) and four out of 121 (3.3%) controls had hyperhomocysteinemia with a statistically significant difference (p < 0.0001). No significant difference was found between IBD patients and controls with regard to the prevalence of homozygotes for the C677T variant (TT) of MTHFR or the prevalence of heterozygotes for the CBS-gene mutation (IN). Among the IBD patients the only independent factor significantly associated with hyperhomocysteinemia was folate deficiency (p = 0.0002), regardless of the MTHFR or the CBS genotype. IBD patients have a higher prevalence of hyperhomocysteinemia than do healthy controls. Folate deficiency is the only independent risk factor in developing hyperhomocysteinemia.

Prevalence of Methylenetetrahydrofolate reductase (MTHFR) C677T polymorphism in Northwest Louisiana newborn population

The Pediatric Genetics laboratory at LSU School of Medicine in Shreveport, LA, began offering prenatal service in NTD and chromosomal defect screening through triple screening program since 1995. The laboratory also began epidemiological research studies on the newborn population of Northwest Louisiana for several genetic disease mutations for the past 4 years as part of March of Dimes birth defects foundation and LSU foundation grants. We have recently reported the gene frequencies for MCAD deficiency, Factor V Leiden in our population and as part of thrombophilia markers we also started investigating the frequencies of MTHFR C677T and prothrombin G20210A polymorphism. Our local population composed of 76% African-Americans, 20% Caucasians, 2% Hispanics, and the rest other ethnic groups. Following English multi-center multivitamin studies on NTD in 1970 and '72 revealing possible risk reduction in recurrences of NTD with periconceptional supplementation of folic acid, folate-activating enzyme, MTHFR, has become the subject of intense study in various diseases. MTHFR was also linked to cardiovascular diseases through hyperhomocystinemia and recently to other complex genetic traits such as Orofacial clefts.In our polymorphism studies, the carrier and homozygous C677T frequencies were found to be 24% and 3.5%, respectively, in the total population. However, on stratification by ethnicity, we found that the hetrozygote and homozygote frequencies were 18%, 46%, 45%, and 0.9%, 21%, 11%, respectively, in African-Americans, Hispanics and Caucasians. Our data found higher C677T homozygotes in our Hispanic newborn population than other ethnic groups and may explain the higher frequency of NTDs and Orofacial Clefts found in this population.