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<i>Background and Objectives</i>: Circadian rhythms have an important implication in numerous physiological and metabolic processes, including the sleep/wake cycle. Inter-individual differences in factors associated with circadian system may be due to gene differences in gene expression. Although several studies have analyzed the association between DNA polymorphisms and circadian variables, the influence on gene expression has been poorly analyzed. Our goal was to analyze the association of genetic variations in the clock genes and the gene expression level. <i>Materials and Methods</i>: We carried out a cross-sectional study of 102 adults (50.9% women). RNA and DNA were isolated from blood and single-nucleotide polymorphisms (SNPs), and the main circadian clock genes were determined. Gene expression of <i>CLOCK</i>, <i>PER1</i>, and <i>VRK2</i> genes was measured by Reverse-transcription polymerase chain reaction (RT-PCR). The association between the DNA-SNPs and gene expression was analyzed at the gene level. In addition, a polygenic risk score (PRS), including all the significant SNPs related to gene expression, was created for each gene. Multivariable model analysis was performed. <i>Results</i>: Sex-specific differences were detected in <i>PER1</i> expression, with these being higher in women (<i>p</i> = 0.034). No significant differences were detected in clock genes expression and lifestyle variables. We observed a significant association between the <i>ARNTL</i>-rs7924734, <i>ARNTL</i>-rs10832027, <i>VRK2</i>- rs2678902 SNPs, and <i>CLOCK</i> gene expression; the <i>PER3</i>-rs228642 and <i>PER3</i>-rs10127838 were related to <i>PER1</i> expression, and the <i>ARNTL</i>-rs10832027, <i>ARNTL</i>-rs11022778, and <i>MNTR1B</i>-rs10830963 were associated with <i>VRK2</i> gene expression (<i>p</i> < 0.05). The specific PRS created was significantly associated with each of the gene expressions analyzed (<i>p</i> < 0.001). Finally, sleep duration was associated with <i>PER3</i>-rs238666 (<i>p</i> = 0.008) and <i>CLOCK</i>-rs4580704 (<i>p</i> = 0.023). <i>Conclusion</i>: We detected significant associations between DNA-SNPs in the clock genes and their gene expression level in leukocytes and observed some differences in gene expression per sex. Moreover, we reported for the first time an association between clock gene polymorphisms and <i>CLOCK</i>, <i>PER1</i>, and <i>VRK2</i> gene expression. These findings need further investigation.