The fat mass and obesity-associated FTO rs9939609 polymorphism is associated with elevated homocysteine levels in patients with multiple sclerosis screened for vascular risk factors
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The previously reported link between homocysteine and obesity, both identified as established risk factors for multiple sclerosis (MS), has not previously been studied in relation to the fat mass and obesity-associated (FTO) gene. Aim: To investigate the mechanism underlying homocysteine accumulation in MS patients. A total of 114 patients and 195 population-matched controls were analysed for the FTO rs9939609 polymorphism. Homocysteine levels were measured in a subgroup of 60 patients and 87 controls screened for multiple vascular risk factors. After adjustment for potential confounders, the risk-associated FTO rs9939609 A-allele was associated with raised homocysteine levels (p = 0.003) in patients diagnosed with MS, but not in controls. Homocysteine levels correlated positively with body mass index (BMI) (p = 0.045) and total cholesterol levels (p = 0.048). Both homocysteine (p = 0.011) and BMI (p = 0.017) were significantly reduced with higher intake of folate in the diet. Higher BMI also correlated with increased intake of saturated/trans fat (p < 0.01) and low physical activity (p < 0.006). Daily intake of at least five fruits and vegetables had a favourable lowering effect on the Expanded Disability Status Scale (EDSS) (p = 0.035), while smoking increased MS disability (p < 0.001). This study has shown for the first time that having a diagnosis of MS moderates the effect of the FTO rs9939609 polymorphism on homocysteine levels. This is consistent with the role of FTO in demethylation and epigenetic changes. Identification of FTO rs9939609 reinforces the importance of adequate fruit, vegetable and folate and restriction of saturated/trans fat intake in the diet.
KeywordsMultiple sclerosis (MS) Homocysteine FTO Obesity Body mass index (BMI)
We gratefully acknowledge the financial support given by the National Health Laboratory Service, the Medical Research Council (MRC) of South Africa and the University of Stellenbosch. The MRC Biostatistics Unit is acknowledged for statistics support. Study participants are acknowledged for their willingness and cooperation to participate in this study.
Disclosure of Potential Conflict of Interest
Professors SJ van Rensburg and MJ Kotze are listed as inventors on patent number 2010/00058. Prof Kotze is also 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. Prof SJ van Rensburg applied the Gknowmix database tool and open innovation genetic testing service delivery model for development of the Demyelinating Diseases GeneScreen™. Together with Dr Frans Cronje, a treatment regimen was developed for application with this genomic solution (patent pending). Registered dietician Mrs Lindiwe Whati developed the nutrition questionnaire used in this study. The remaining authors declared no conflict of interest. No writing assistance was utilised in the preparation of this manuscript.
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