Investigation of FTO Gene-BMI Association in a Romanian Sample: a Functional Genomic Interpretation

Abstract

Previously, we reported the results of an investigation regarding the FTO gene variant rs 1421085 association with BMI in a randomly selected Romanian sample, which showed a statistically relevant relationship. However, the small sample volume could not permit highlighting the hypothesized age factor role; the scarce literature information did not permit comments regarding the functional link between gene variation and BMI values. The actual work recapitulated the BMI-FTO association on an extended sample volume to 167, added the FTOrs17817449 variant, which has been reported in LD with the initial genotype, and approached a different statistical analysis (both of the separate and combined genotypes). The new results statistically confirmed the positive BMI-FTO association (p=0.018 and p=0.03 for each genotype rs1421085 and rs17817449, respectively p=0.03 for combined genotypes T/G and T/C, respectively); also, the age factor analysis showed the greater the age (after 40), the more tendency to gain weight (χ2=8.63). The observed high frequency of the risk rs1421805 genotype in our population and the age factor role in the FTO-BMI association are commented in the view of the newly emerged hypothesis regarding the climate influence on human migration during evolution and FTO polymorphic genotype distribution globally. Recent literature reports on the complex chromatin structure of the FTO locus, which environmental factors may influence, and on the FTO protein activity as an m6A demethylase are used in interpreting the biological role of this gene in adipose tissue formation, its maintenance, and lipolysis processes.