Abstract
BackgroundLow 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.MethodsA 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.ResultsThe 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.ConclusionThe 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.
Highlights
Obesity and its related comorbidities are leading causes of mortality and morbidity worldwide [1]
No significant difference between obese and non-obese individuals were observed in the levels of fasting glucose, insulin, HbA1c, folic acid, homocysteine, vitamin B12 and waist to hip ratio (P>0.05)
The baseline characteristics which compares individuals with Normal Glucose Tolerance (NGT), pre-diabetes, and T2D is shown in Additional file 1: Table S1
Summary
Obesity and its related comorbidities are leading causes of mortality and morbidity worldwide [1]. A recent pooled analysis of 19 studies found no evidence for an inverse relationship between vitamin B12 and BMI levels and reported that the majority of observational studies had a high risk of bias and heterogeneity due to the fact that most of the studies were not designed to investigate the association between B12 level and BMI [18]. In light of these findings, using a genetic approach to explain the genetic mechanisms for obesity and its link with vitamin B12 concentrations could be a better option, in terms of reducing any influence from unmeasured confounding factors. 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
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