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Significance of dietary folate intake, homocysteine levels and MTHFR 677 C>T genotyping in South African patients diagnosed with depression: test development for clinical application

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Abstract

Low folate intake in the presence of the functional MTHFR 677 C > T (rs1801133) polymorphism is an important cause of elevated homocysteine levels previously implicated in major depressive disorder (MDD) and many other chronic diseases. In this study the clinical relevance and inter-relationship of these aspects were evaluated in 86 South African patients diagnosed with MDD and 97 population-matched controls participating in a chronic diseases screening program. A questionnaire-based clinical and nutrition assessment was performed, homocysteine levels determined, and all study participants genotyped for MTHFR 677 C > T (rs1801133) using allele-specific TaqMan technology. The folate score was found to be significantly lower in the patient group compared to controls (p = 0.003) and correlated with increased body mass index (BMI), particularly in females with MDD (p = 0.009). BMI was significantly higher in the MDD patients compared with controls after adjustment for age and sex (p = 0.015), but this association was no longer significant after further adjustment for the level of folate intake in the diet. In MDD patients but not controls, the minor T-allele of MTHFR 677 C > T was associated with increased BMI (p = 0.032), which in turn correlated significantly with increased homocysteine levels. The significant association between BMI and homocysteine levels was observed in both the MDD patient (p = 0.049) and control (p = 0.018) study groups. The significantly higher homocysteine levels observed in MDD patients compared to controls after adjustment for age and sex (p = 0.030), therefore appears to be mediated by the effects of MTHFR 677 C > T and low folate intake on BMI. Detection of the low-penetrance MTHFR 677 C > T mutation reinforces the importance of folate intake above the recommended daily dose to prevent or restore dysfunction of the methylation pathway.

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Acknowledgments

We gratefully acknowledge the financial support from Winetech and the Technology for Human Resources and Industry Program (THRIP). The MRC Biostatistics Unit is acknowledged for statistics support. Drs Karien Botha and Hilmar Luckhoff are thanked for providing clinical support and Lindiwe Whati for development of the nutrition and lifestyle questionnaire.

Disclosure

Prof Kotze is a director and shareholder of Gknowmix (Pty) Ltd. that has developed a database tool for research translation under the auspices of the Innovation Centre of the South African Medical Research Council. The other authors declared no conflict of interest and no writing assistance was obtained in the preparation of this manuscript.

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Authors and Affiliations

  1. Division of Chemical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa

    Darnielle Delport & Renata Schoeman

  2. Division of Anatomical Pathology, Department of Pathology, Faculty of Medicine and Health Sciences, Stellenbosch University, Tygerberg, South Africa

    Nicole van der Merwe, Leslie R. Fisher, Dieter Geiger & Maritha J. Kotze

  3. Department of Molecular Biology and Human Genetics, Stellenbosch University, Tygerberg, South Africa

    Lize van der Merwe

  4. Department of Statistics, University of the Western Cape, Cape Town, Western Cape, South Africa

    Lize van der Merwe

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  1. Darnielle Delport
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  2. Renata Schoeman
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  3. Nicole van der Merwe
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  4. Lize van der Merwe
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  7. Maritha J. Kotze
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Correspondence to Maritha J. Kotze.

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Delport, D., Schoeman, R., van der Merwe, N. et al. Significance of dietary folate intake, homocysteine levels and MTHFR 677 C>T genotyping in South African patients diagnosed with depression: test development for clinical application. Metab Brain Dis 29, 377–384 (2014). https://doi.org/10.1007/s11011-014-9506-7

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