[Variability of the genetic marker CLOCK rs3749474 and its impact on research and clinical trials on obesity and circadian rhythm].

Introduction: circadian rhythms influence eating behavior, with the CLOCK gene being one of those responsible for its regulation. The rs3749474T/C of the CLOCK gene has been associated with an increased risk of obesity. Those who carry the T allele have greater weight loss on a diet low in carbohydrates and lipids than those who have the CC form. Methodology: using the 1000 Genomes database, the genotype of the single nucleotide polymorphism (SNP) rs3749474 was obtained from 2,504 individuals, covering five macro-populations (Africa, East Asia, South Asia, Europe and Latin America) and 26 populations. CT and TT were treated as non-risk genotypes and CC as risk. Fisher's exact test was used to compare the frequencies of risk and non-risk genotypes among the five macro populations. Results: there is a high differentiation for the frequency of genotypes carrying the T allele among the macro-populations: Africa reached only 31.47 %, Europe 56.86 %; Latin America 66.28 %; South Asia 68.3 % and East Asia 81.15 %, with significant differences (pFisher < 0.05) in all comparisons, except between Latin America and South Asia. Low heterogeneity was observed between populations within each macro population. Conclusions: the high heterogeneity for the genotypic frequencies of CLOCK rs3749474 in the studied macro-populations indicates that the decrease in the consumption of carbohydrates and lipids will have a heterogeneous impact, from the epidemiological point of view. This suggests including the genetic ancestry in later studies of association between circadian cycles, eating behavior and obesity, in order to develop personalized clinical tests.