European Collaborative Group of the IMMIDIET Project. Association between MTHFR C677T genotype and circulating folate levels irrespective of folate intake: data from the IMMIDIET Project

Research Laboratories, Fondazione di Ricerca e Cura "Giovanni Paolo II", Catholic University, Campobasso, Italy and National Reference Centre for Familial Hyperlipoproteinemias and Faculty of Nursing and Health Professional Studies, Slovak Medical University, Bratislava, Slovakia.
Nutrition (Impact Factor: 2.93). 11/2011; 27(11-12):1209-10. DOI: 10.1016/j.nut.2011.07.008
Source: PubMed
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    • "However, results of folate or homocysteine levels in blood in relation to the MTHFR genotype are conflicting. There are several studies showing circulating high levels of homocysteine and low levels of folate in subjects with the TT genotype of C677T (Ma et al., 1999; Vohnout et al., 2011; Zappacosta et al., 2014), along with many other studies indicating a lack of association (Bjelland et al., 2003; Mischoulon et al., 2012; Moorthy et al., 2012; Lok et al., 2014). "
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    ABSTRACT: Methylenetetrahydrofolate reductase (MTHFR) genetic variations have been widely studied in major depressive disorder (MDD) and antidepressants outcome. An interaction with catechol-O-methyltransferase (COMT) has also been proved affecting depression. The aim of this study was to clarify the role of the most commonly studied single nucleotide polymorphisms (SNPs) of MTHFR gene in MDD and in treatment response mechanisms, along with the impact of the interaction with COMT. A total of 613 MDD patients, of whom 389 were classified as having treatment resistant depression (TRD), and 463 controls were enrolled. The A1298C, C677T and COMT Val158Met were genotyped. Genetic data were integrated with a transcriptional level analysis in peripheral blood cells (PBCs) and fibroblasts. The A1298C CC homozygotes were more frequent in MDD patients compared to controls in women, increasing twice the genetic risk to develop depression. Moreover this genotype resulted in epistasis with COMT Met carriers in association with MDD. No significant effects were obtained concerning response to treatment. Transcriptional analyses highlighted a strong correlation between the mRNA levels of MTHFR in fibroblasts and COMT genotypes whereas no significant association with MDD was found. PBCs results revealed relevant influences of environmental factors. We did not measure folate and homocisteine levels. This study showed the involvement of A1298C, Val158Met and their interaction in MDD. The transcriptional analyses supported the participation of COMT in the folate pathway, which partakes in the complex network of gene×gene and gene×environment interactions of MDD etiopathogenesis. Copyright © 2015 Elsevier B.V. All rights reserved.
    Full-text · Article · May 2015 · Journal of Affective Disorders
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    • "To protect against selection bias, the selection of eligible pairs was randomized in each center. Between October 2001 and October 2003, 271 pairs in the Abruzzo region in Italy and 263 in southwest London ages 26 to 64 y (mean AE SD, men 48 AE 7, women 45 AE 7) were randomly enrolled [13] [14]. The participation rates were 85% in Italy and 90% in London. "
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    ABSTRACT: Objective Folate status has been associated with neural tube defects and cerebrovascular disease. We aimed at evaluating possible differences in folate status in two EU Countries and to assess their possible association with dietary patterns and/or other lifestyles. Methods and Procedures In the framework of the EU-funded IMMIDIET Project, 1,068 subjects (534 man-woman pairs), aged 26-64 years, were enrolled in Italy and UK. 1-year-recall Food Frequency Questionnaire was used to evaluate dietary intake. Reduced Rank Regression-analysis was used to derive a dietary pattern better describing high dietary folate intake. Results 11.3% of the Italians and 45.1% of the British exceeded the optimal dietary folate intake of 400μg/day (Recommended Dietary Allowance). 66.7% and 22.1% of Italian and UK women, respectively, all at childbearing age, had folate serum levels lower than 6.62ng/ml (P=0.01). The percentage of total variance of dietary folate intake explained by food group consumption was 14.2% and 16.3% in Italy and UK, respectively. Reduced Rank Regression-analysis indicated a healthy pattern which was positively associated with folate serum levels in both Countries (for all β-coef>0, P<0.001):100μg/day increase in dietary folate intake was associated with 13.8% and 10.5% increase in folate serum levels in the Italian and English population, respectively (for 100μg/day increase eβ-coef=1.138 and 1.105, P<0.001). Smoking habit was negatively but physical activity positively associated with folate serum levels (P<0.05). Conclusion(s) An inadequate dietary folate intake and subsequent serum levels were observed in Italian subjects. High consumption of food sources of folate was positively associated with folate serum levels, explaining a good proportion of its variability.
    Full-text · Article · Jan 2013 · Nutrition
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    ABSTRACT: The present study enrolled 251 diabetic patients, including 101 with neuropathy and 150 without neuropathy. Of the 150 patients, 100 had no complications, such as retinopathy, nephropathy, or neuropathy. Polymerase chain reaction-restriction fragment length polymorphism analysis was used to identify methylenetetrahydrofolate reductase gene variants. Plasma homocysteine levels were also measured. Homocysteine levels and the frequency of hyperhomocysteinemia were significantly higher in patients with diabetic peripheral neuropathy compared with diabetic patients without neuropathy (P < 0.05). In logistic regression analysis with neuropathy as the dependent variable, the frequency of C677T in methylenetetrahydrofolate reductase was significantly higher in patients with diabetic peripheral neuropathy compared with patients without diabetic complications. Homocysteine levels were significantly higher in patients with diabetic peripheral neuropathy carrying the 677T allele and low folic acid levels. In conclusion, hyperhomocysteinemia is an independent risk factor for diabetic neuropathy in Chinese patients with diabetes. The C677T polymorphism in methylenetetrahydrofolate reductase and low folic acid levels may be risk factors for diabetic peripheral neuropathy in Chinese patients with diabetes.
    No preview · Article · Oct 2012 · Neural Regeneration Research
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