Background Low vitamin B12 concentrations have been associated with major clinical outcomes, including adiposity, in Indian populations. The Fat mass and obesity-associated gene (FTO) is an established obesity-susceptibility locus; however, it remains unknown whether it influences vitamin B12 status. Hence, we investigated the association of two previously studied FTO polymorphisms with vitamin B12 concentrations and metabolic disease-related outcomes and examined whether these associations were modified by dietary factors and physical activity. Methods A total of 176 individuals with type 2 diabetes, 152 with pre-diabetes, and 220 normal glucose-tolerant individuals were randomly selected from the Chennai Urban Rural Epidemiology Study. Anthropometric, clinical, and biochemical investigations, which included body mass index (BMI), waist circumference, vitamin B12, homocysteine, and folic acid were measured. A validated food frequency questionnaire was used for dietary assessment and self-reported physical activity measures were collected. An unweighted genetic risk score (GRS) was calculated for two FTO single-nucleotide polymorphisms (rs8050136 and rs2388405) by summation of the number of risk alleles for obesity. Interaction analyses were performed by including the interaction terms in the regression model. Results The GRS was significantly associated with increased BMI (P = 0.009) and risk of obesity (P = 0.023). Individuals carrying more than one risk allele for the GRS had 13.13% lower vitamin B12 concentrations, compared to individuals carrying zero risk alleles (P = 0.018). No associations between the GRS and folic acid and homocysteine concentrations were observed. Furthermore, no statistically significant GRS-diet or GRS-physical activity interactions with vitamin B12, folic acid, homocysteine or metabolic-disease outcomes were observed. Conclusion The study shows for the first time that a genetic risk score using two FTO SNPs is associated with lower vitamin B12 concentrations; however, we did not identify any evidence for the influence of lifestyle factors on this association. Further replication studies in larger cohorts are warranted to investigate the association between the GRS and vitamin B12 concentrations.

中文翻译：

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亚裔印度人群中 FTO 基因变异与维生素 B12 浓度之间关联的证据。


背景 在印度人群中，低维生素 B12 浓度与主要临床结果（包括肥胖）相关。脂肪量和肥胖相关基因（FTO）是一个已确定的肥胖易感基因座；然而，尚不清楚它是否会影响维生素 B12 的状态。因此，我们研究了先前研究的两个 FTO 多态性与维生素 B12 浓度和代谢疾病相关结果的关联，并检查了这些关联是否会受到饮食因素和体力活动的影响。方法从钦奈城乡流行病学研究中随机抽取176名2型糖尿病患者、152名糖尿病前期患者和220名正常糖耐量患者。人体测量、临床和生化研究，包括测量体重指数 (BMI)、腰围、维生素 B12、同型半胱氨酸和叶酸。使用经过验证的食物频率调查问卷进行饮食评估，并收集自我报告的身体活动指标。通过肥胖风险等位基因数量的总和，计算两个 FTO 单核苷酸多态性（rs8050136 和 rs2388405）的未加权遗传风险评分（GRS）。通过在回归模型中包含交互项来进行交互分析。结果 GRS 与 BMI 增加（P = 0.009）和肥胖风险（P = 0.023）显着相关。与携带零风险等位基因的个体相比，携带多个 GRS 风险等位基因的个体维生素 B12 浓度降低 13.13% (P = 0.018)。没有观察到 GRS 与叶酸和同型半胱氨酸浓度之间的关联。 此外，没有观察到 GRS-饮食或 GRS-身体活动与维生素 B12、叶酸、同型半胱氨酸或代谢疾病结果之间存在统计学显着的相互作用。结论 该研究首次表明，使用两个 FTO SNP 进行的遗传风险评分与较低的维生素 B12 浓度相关；然而，我们没有发现任何证据证明生活方式因素对这种关联的影响。有必要在更大的队列中进行进一步的重复研究，以调查 GRS 和维生素 B12 浓度之间的关联。