<abstract xmlns="http://www.w3.org/1999/xhtml"><bold>Objective</bold>: Methylene-tetrahydrofolate reductase (MTHFR) is involved in adapting metabolism to environmental challenges by various mechanisms, including the control of gene expression by epigenetic and post-translational changes of transcription factors. Though a metabolic syndrome candidate gene, association studies of its common polymorphism rs1801133 (MTHFR-Ala222Val) remain inconclusive with important ethnic differences, and the effect on disease progression was not addressed.<bold>Methods</bold>: 307 middle-aged metabolic syndrome patients in a central Romanian hospital setting were investigated metabolically, and genotyped by PCR-RFLP. Disease progression was assessed by the age of onset of metabolic components, as well as development of non-alcoholic fatty liver disease and atherosclerotic complications.<bold>Results</bold>: The minor allele frequency of rs1801133 was 30.13%. Metabolic parameters showed no statistically significant differences according to genotype, but variant carriers developed dysglycemia and dyslipidemia earlier (53.28±10.8 vs 59.44±9.31 years, p&lt;0.05 and 58.57±11.31 vs 64.72±10.6 years, p&lt;0.1).While the polymorphism did not influence hepatic complications, an inverse association was found for manifest atherosclerosis (OR=0.49, p=0.006, 95%CI:0.29-0.81), which may be folate-status dependent, and needs further investigations. Simultaneous analysis with transcription factor polymorphisms (rs1801282, rs8192678) showed that the more protective genotypes were present the later metabolic disturbances developed, and in the presence of the other two variants the apparent protective cardiovascular effect disappeared.<bold>Conclusions</bold>: The common functional polymorphism rs1801133 may influence metabolic syndrome progression, the age of onset of components and development of atherosclerotic complications. Besides simple additive effects, complex mitigating and aggravating variant interactions may exist, and the protective or predisposing outcome may depend on modifiable environmental factors.</abstract>

Objective: Methylene-tetrahydrofolate reductase (MTHFR) is involved in adapting metabolism to environmental challenges by various mechanisms, including the control of gene expression by epigenetic and post-translational changes of transcription factors. Though a metabolic syndrome candidate gene, association studies of its common polymorphism rs1801133 (MTHFR-Ala222Val) remain inconclusive with important ethnic differences, and the effect on disease progression was not addressed.Methods: 307 middle-aged metabolic syndrome patients in a central Romanian hospital setting were investigated metabolically, and genotyped by PCR-RFLP. Disease progression was assessed by the age of onset of metabolic components, as well as development of non-alcoholic fatty liver disease and atherosclerotic complications.Results: The minor allele frequency of rs1801133 was 30.13%. Metabolic parameters showed no statistically significant differences according to genotype, but variant carriers developed dysglycemia and dyslipidemia earlier (53.28±10.8 vs 59.44±9.31 years, p<0.05 and 58.57±11.31 vs 64.72±10.6 years, p<0.1).While the polymorphism did not influence hepatic complications, an inverse association was found for manifest atherosclerosis (OR=0.49, p=0.006, 95%CI:0.29-0.81), which may be folate-status dependent, and needs further investigations. Simultaneous analysis with transcription factor polymorphisms (rs1801282, rs8192678) showed that the more protective genotypes were present the later metabolic disturbances developed, and in the presence of the other two variants the apparent protective cardiovascular effect disappeared.Conclusions: The common functional polymorphism rs1801133 may influence metabolic syndrome progression, the age of onset of components and development of atherosclerotic complications. Besides simple additive effects, complex mitigating and aggravating variant interactions may exist, and the protective or predisposing outcome may depend on modifiable environmental factors.

MTHFR - Ala222Val Effects on Metabolic Syndrome Progression

University of Medicine and Pharmacy Tirgu Mures

Acta Marisiensis - Seria Medica

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

{"article-title":"MTHFR - Ala222Val Effects on Metabolic Syndrome Progression"}

Objective: Methylene-tetrahydrofolate reductase (MTHFR) is involved in adapting metabolism to environmental challenges by various mechanisms, including the...

MTHFR - Ala222Val Effects on Metabolic Syndrome Progression

Published Online: Jul 07, 2018

Page range: 64 - 69

Received: May 11, 2018

Accepted: Jun 12, 2018

DOI: https://doi.org/10.2478/amma-2018-0009

Keywords
metabolic syndrome X, atherosclerosis, non-alcoholic fatty liver disease, methylenetetrahydrofolate reductase, genetic polymorphism

© 2018 Katalin Csép et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

MTHFR - Ala222Val Effects on Metabolic Syndrome Progression

Published Online: Jul 07, 2018

Page range: 64 - 69

Received: May 11, 2018

Accepted: Jun 12, 2018

DOI: https://doi.org/10.2478/amma-2018-0009

Keywordsmetabolic syndrome X, atherosclerosis, non-alcoholic fatty liver disease, methylenetetrahydrofolate reductase, genetic polymorphism

© 2018 Katalin Csép et al., published by Sciendo

This work is licensed under the Creative Commons Attribution-NonCommercial-NoDerivatives 3.0 License.

Keywords
metabolic syndrome X, atherosclerosis, non-alcoholic fatty liver disease, methylenetetrahydrofolate reductase, genetic polymorphism