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
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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DOI：
10.1007/s11011-014-9486-7
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发表时间：
2014-06-01
影响因子：
3.6
通讯作者：
Kotze, Maritha J.
中科院分区：
文献类型：
--
作者：
Davis, Wiliam;van Rensburg, Susan J.;Kotze, Maritha J.
先前报道的同型半胱氨酸和肥胖之间的联系，都被确定为多发性硬化症（MS）的危险因素，以前没有研究过与脂肪量和肥胖相关（FTO）基因。目的：探讨代谢综合征患者同型半胱氨酸蓄积的机制。共有114名患者和195名人群匹配的对照进行了FTO rs 9939609多态性分析。在60名患者和87名对照者的亚组中测量了同型半胱氨酸水平，这些患者和对照者筛选了多种血管危险因素。校正潜在混杂因素后，风险相关的FTO rs 9939609 A等位基因与MS患者同型半胱氨酸水平升高相关（p = 0.003），但在对照组中不相关。同型半胱氨酸水平与体重指数（BMI）（p = 0.045）和总胆固醇水平（p = 0.048）呈正相关。随着饮食中叶酸摄入量的增加，同型半胱氨酸（p = 0.011）和BMI（p = 0.017）均显著降低。较高的BMI还与饱和/反式脂肪摄入量增加（p < 0.01）和体力活动减少（p < 0.006）相关。每天摄入至少五种水果和蔬菜对扩展残疾状态量表（EDSS）有有利的降低作用（p = 0.035），而吸烟增加了MS残疾（p < 0.001）。这项研究首次表明，MS的诊断缓和了FTO rs 9939609多态性对同型半胱氨酸水平的影响。这与FTO在去甲基化和表观遗传变化中的作用一致。FTO rs 9939609的鉴定加强了饮食中充足水果、蔬菜和叶酸以及限制饱和/反式脂肪摄入的重要性。
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.