Sex-dependent Association of Central Circadian Clock Gene Polymorphisms with Clinical Risk Markers for Noncommunicable Diseases in the Young Population

Background: The circadian clock, which governs periodic physiological changes, is influenced by various environmental factors, and its disruptions can lead to non-communicable chronic diseases (NCDs). Among the genes that control the circadian clock are ARNTL, CLOCK, CRY1, PER1, PER2, NR1D2, and MTNR1B, with several polymorphisms associated with diseases such as diabetes and hypertension. Therefore, this study aimed to determine the association between SNPs in the aforementioned genes and markers of non-communicable chronic diseases (NCDs) in a young population, stratified by gender.

Methods: A sample of 346 individuals of both sexes aged 18 to 27 underwent clinical and nutritional evaluations to determine clinical markers associated with NCDs. Using isothermal PCR, 119 polymorphisms in the ARNTL, CLOCK, CRY1, PER1, PER2, NR1D2, and MTNR1B genes were determined. Subsequently, binary logistic regression analyses and mean comparisons using Student's t-test and one-way ANOVA with Bonferroni adjustment were performed.

Results: Polymorphisms were associated with risk factors such as elevated waist circumference, BMI, insulin, and lipid imbalances, while some acted protectively. Notable SNPs included rs6486122, rs77486964, rs11022756, rs72869158 from ARNTL; rs7309618, rs10778528 from CRY1; rs2304911 from PER1; rs72620839, rs58574366 from PER2; rs6832769, rs1056547 from CLOCK; and rs4858095, rs11922577 from NR1D2, providing insights into the associations of genetic markers with clinically relevant markers for NCDs.

Conclusion: Clock gene polymorphisms exhibit associations with clinical markers of NCDs, emphasizing the intricate interaction between the biological clock and risk factors. This underscores the importance of genetic testing and personalized clinical approaches for prevention and treatment. Further research is needed to understand the underlying mechanisms and long-term health impacts of these genetic variations.