title: 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.
abstract: 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.
  
  
  OBJECTIVE
  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.
authors: Division of Chemical Pathology, Department of Pathology, National Health Laboratory Service (NHLS) and Faculty of Medicine and Health Sciences, Stellenbosch University, Cape Town, South Africa, williamdavis13@gmail.com.
authors: Wiliam
authors: W
authors: Davis
authors: Susan J
authors: SJ
authors: van Rensburg
authors: Frans J
authors: FJ
authors: Cronje
authors: Lindiwe
authors: L
authors: Whati
authors: Leslie R
authors: LR
authors: Fisher
authors: Lize
authors: L
authors: van der Merwe
authors: Dieter
authors: D
authors: Geiger
authors: M Shafick
authors: MS
authors: Hassan
authors: Tandi
authors: T
authors: Matsha
authors: Rajiv T
authors: RT
authors: Erasmus
authors: Maritha J
authors: MJ
authors: Kotze
mesh_terms: D000328:Adult; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; D015415:Biomarkers / Q000097:blood; D005260:Female; D005500:Follow-Up Studies; D006710:Homocysteine / Q000097:blood; D006801:Humans; D008297:Male; D008875:Middle Aged; D009103:Multiple Sclerosis / Q000097:blood / Q000175:diagnosis / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*; D011506:Proteins / Q000235:genetics*; D012189:Retrospective Studies; D012307:Risk Factors; D040242:Risk Reduction Behavior; D014652:Vascular Diseases / Q000097:blood / Q000175:diagnosis / Q000235:genetics*
chemical_list: D015415:Biomarkers; D011506:Proteins; D006710:Homocysteine; D000071516:Alpha-Ketoglutarate-Dependent Dioxygenase FTO; C526492:FTO protein, human