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

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.

Homocysteine as a peripheral biomarker in bipolar disorder: A meta-analysis

“…Of those, we excluded 2540 on the basis of title and abstract. We went through 57 full-text articles of which: two were excluded because they were duplicates of included studies with overlapping samples [61,62]; eighteen studies were excluded because they lacked a control group [38,46,[63][64][65][66][67][68][69][70][71][72][73][74][75][76][77][78]; twelve were excluded because they were not performed in subjects with a diagnosis of BD [41,[79][80][81][82][83][84][85][86][87][88][89]; twelve were excluded because they did not measure Hcy levels [90][91][92][93][94][95][96][97][98][99][100][101]; and two were excluded because they presented mixed data on BD and other psychiatric disorders [102,103]. The authors of a study that analysed together the total me...…”

MTHFR: Genetic variants, expression analysis and COMT interaction in major depressive disorder

“…In fact several variables, such as medications (e.g., antibiotics, oral contraceptives, and some anticancer agents), lifestyle (e.g., dietary habits, smoking, and alcohol consume) and socio-demographical characteristics (e.g., age, gender, and ethnicity) have an effect on folate metabolism (Reif et al, 2005;Delport et al, 2014;Lok et al, 2014;Zappacosta et al, 2014).…”

Exome Sequencing in a Family with Luminal-Type Breast Cancer Underpinned by Variation in the Methylation Pathway

“…Both the index patient and her affected 29-year old daughter tested positive for MTHFR 677 C>T, investigated in this study as a potential contributing factor for breast cancer development against a possible genetic background of rare variants that may be uncovered by WES. In this family with inherited breast cancer, both the daughter (BMI 27.5 kg/m 2 ) and her mother (BMI 27.8 kg/m 2 ) were overweight with suboptimal intake of folate-rich food in the diet (folate score < 14) according to the nutrition and lifestyle assessment performed as previously described by Delport et al [27]. The presence of BRCA1 and BRCA2 mutations was largely excluded as the cause of familial breast cancer using NGS and multiplex ligation-dependent probe amplification (MLPA) at a commercial laboratory (NewGene, Newcastle, UK).…”

“…The low-penetrance MTHFR 677 C>T mutation found to be associated with hormone receptor positive breast cancer [15], has previously been linked with increased BMI in South African patients diagnosed with major depressive disorder [27]. A low folate score, as reflected by the nutrition questionnaire used by Delport et al [27], correlated with increased BMI and risk of depression in South African patients with the MTHFR 677 C>T mutation.…”

“…A low folate score, as reflected by the nutrition questionnaire used by Delport et al [27], correlated with increased BMI and risk of depression in South African patients with the MTHFR 677 C>T mutation. Depression is a major comorbidity in breast cancer survivors and impacts on both the quality of life and treatment decision making.…”