Role of treatment-modifying MTHFR677C>T and 1298A>C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy
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Francisco J. Jiménez-Ramírez
Abstract
Background:
The study was conducted to investigate potential association between MTHFR genotypes and diabetic peripheral neuropathy (DPN) in Puerto Ricans with type-2 diabetes mellitus (T2DM) treated with metformin. The prevalence of major MTHFR polymorphisms in this cohort was also ascertained.
Methods:
DNAs from 89 metformin-treated patients with T2DM and DPN were genotyped using the PCR-based RFLP assay for MTHFR677C>T and 1298A>C polymorphisms. Frequency distributions of these variants in the study cohort were compared to those reported for three reference populations (HapMap project) and controls (400 newborn specimens). Chi-square (or Fischer’s exact) tests and odds ratios (OR) were used to assess association with DPN susceptibility risk (patients vs. controls) and biochemical markers (wild types vs. carriers).
Results:
Sixty-seven percent (67%) of participants carry at least one of these MTHFR polymorphisms. No deviations from Hardy-Weinberg equilibrium were detected. The genotype and allele frequencies showed statistically significant differences between participants and controls (p<0.0001 and p=0.03, respectively). Results suggest that 1298A>C but not 677C>T is associated with DPN susceptibility in this cohort (p=0.018). Different patterns of allelic dissimilarities are observed when comparing our cohort vs. the three parental ancestries. After sorting individuals by their carrier status, no significant associations were observed between these genetic variants (independently or combined) and any of the biochemical markers (HbA1c, folate, vitamin B12, homocysteine).
Conclusions:
Prevalence of major MTHFR variants in Puerto Rican patients with T2DM is first time ever reported. The study provides further evidence on the use of this genetic marker as an independent risk factor for DPN.
Acknowledgments
The material presented herein is the result of work supported with resources from and the use of facilities for performing genetic assays at the UPR-MSC RCMI Center for Genomics in Health Disparities and Rare Disorders. The authors also want to thank Miguel Ayala, Luis A Robles de Jesus, Hasna Abboud-Chalhoub, Zoriely Amador-Ríos, Edmarielis González-González, Isaúl Hernández-Diaz, Ana P. Lozada-Barea, Brenda I. Méndez-Guzmán, Nydia A. Moreno-Rivera, Vanessa G. Pozzi-Lorenzo, Rafael E. Ramos-Franco, Jomir Rivera-Rivera, Ivonne M. Rosario-Calderon, Beverly N. Santos-Sierra, and Glendalis Vargas-Vargas for their help in this survey. Finally, we want to thank all the patients for their participation in this study.
Author contributions: All the authors have accepted responsibility for the entire content of this submitted manuscript and approved submission.
Research funding: This investigation was supported in part by the Research Center in Minority Institutions (RCMI) grants from the National Center for Research Resources (2G12-RR003051) and the National Institute on Minority Health and Health Disparities (8G12-MD007600) of the National Institutes of Health (NIH). The content is solely the responsibility of the authors and does not necessarily represent the official views of the NIH, owners, and employees at Farmacia San José or the United States government. Authors have no relevant affiliation or financial involvement with any organization or entity with a financial interest in or conflicts of interest with the subject matter or materials discussed in the article that need to be disclosed. No writing assistance was utilized in the production of this manuscript.
Employment or leadership: None declared.
Honorarium: None declared.
Competing interests: The funding organization(s) played no role in the study design; in the collection, analysis, and interpretation of data; in the writing of the report; or in the decision to submit the report for publication.
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©2017 Walter de Gruyter GmbH, Berlin/Boston
Artikel in diesem Heft
- Frontmatter
- Review
- Review of pharmacogenetics studies of L-asparaginase hypersensitivity in acute lymphoblastic leukemia points to variants in the GRIA1 gene
- Population Pharmacogenomics
- Genetic polymorphisms of cytochrome P450 enzymes: CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in the Croatian population
- Original Articles
- Role of treatment-modifying MTHFR677C>T and 1298A>C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy
- Genotyping CYP2D6 by three different methods: advantages and disadvantages
- Relationship between metabolic phenotypes and genotypes of CYP1A2 and CYP2A6 in the Nigerian population
- Influence of genetic polymorphisms of CYP3A5 and ABCB1 on sirolimus pharmacokinetics, patient and graft survival and other clinical outcomes in renal transplant
- Cytotoxicity and cytochrome P450 inhibitory activities of Clinacanthus nutans
- Verification of propofol sulfate as a further human propofol metabolite using LC-ESI-QQQ-MS and LC-ESI-QTOF-MS analysis
Artikel in diesem Heft
- Frontmatter
- Review
- Review of pharmacogenetics studies of L-asparaginase hypersensitivity in acute lymphoblastic leukemia points to variants in the GRIA1 gene
- Population Pharmacogenomics
- Genetic polymorphisms of cytochrome P450 enzymes: CYP2C9, CYP2C19, CYP2D6, CYP3A4, and CYP3A5 in the Croatian population
- Original Articles
- Role of treatment-modifying MTHFR677C>T and 1298A>C polymorphisms in metformin-treated Puerto Rican patients with type-2 diabetes mellitus and peripheral neuropathy
- Genotyping CYP2D6 by three different methods: advantages and disadvantages
- Relationship between metabolic phenotypes and genotypes of CYP1A2 and CYP2A6 in the Nigerian population
- Influence of genetic polymorphisms of CYP3A5 and ABCB1 on sirolimus pharmacokinetics, patient and graft survival and other clinical outcomes in renal transplant
- Cytotoxicity and cytochrome P450 inhibitory activities of Clinacanthus nutans
- Verification of propofol sulfate as a further human propofol metabolite using LC-ESI-QQQ-MS and LC-ESI-QTOF-MS analysis
