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

Abstract

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 sug-gests including the genetic ancestry in later studies of association between circadian cycles, eating behavior and obesity, in order to develop personalized clinical tests.