Comprehensive Assessment of the Effect of Single Nucleotide Polymorphism of the CLOCK Gene rs1801260 on the Development of Metabolic Disorders in Obese Individuals
Authors: Nelaeva Ju.V. ,   Tyumen State Medical University, Naimushina A.G. , Nelaeva A.A. , Vostrikova A.A. , Novopashina N.S. , Verholanceva A.A. , Vedernikova S.A. ,   Multidisciplinary Consultative and Diagnostic Center, Tyumen
Published: July 2024

Aim – to conduct a comprehensive assessment of the impact of single nucleotide polymorphism of the CLOCK rs1801260 gene on the development of metabolic disorders in obese individuals. Material and methods. We examined 150 people with signs of chronic desynchronosis and obesity of the first degree according to the criteria of the World Health Organization (body mass index (BMI) – 30.0–34.9 kg/m2) aged 45 to 59 years. The chronobiological component and sleep quality were assessed based on the results of the Horn – Ostberg test, the Pittsburgh Sleep Quality Index (PSQI), the Munich Chronotype Test and cosinor-analysis of glycemia. Genotyping of samples of polymorphic markers of the key biological clock gene CLOCK rs1801260 using real-time polymerase chain reaction iCycler Real Time Systemс with iQ5 Manager software from Bio-Rad Laboratories Inc. (Hercules, CA, USA). An anthropometric study, blood pressure measurement, study of the glycemic profile on an empty stomach and 2 hours after a meal were carried out using the glucose oxidase method on a BIOSEN C_line device (Germany), and glycated hemoglobin was determined using the high-performance liquid chromatography method on a D-10 Bio-Rad analyzer (USA). Lipid profile indicators were measured on an automatic biochemical analyzer SAPPHIRE 400. Research. 85% of the patients examined complained of poor sleep quality and frequent awakenings. Night sleep was only 6:20 ± 0:14 with a confidence interval of 6:25–6:32. Amplitude-phase indicators of glycemia also indicated the presence of desynchronosis. In persons with degree I obesity without carbohydrate metabolism disorders with the TC CLOCK genotype, a higher BMI of 32.5 kg/m2 was revealed, which is 1.8% more than in carriers of the CC genotype, and 4% exceeds the BMI of carriers of the TT genotype (p = 0.001). In carriers of the heterozygous genotype TC CLOCK, the average waist circumference (WC) was 102 cm, in contrast to homozygotes TT (WC – 99 cm (p = 0.001)) and CC (WC – 96 cm (p = 0.001)). Based on the results of the analysis of the PSQI, it was found that unsatisfactory assessment of sleep quality predominated in individuals heterozygous for the TC genotype. The correlation between CLOCK and an increase in WC (r = 0.712, p = 0.001), CLOCK and evening chronotype (r = 0.754, p = 0.001) indicated an unfavorable course of obesity in carriers of the TC genotype and a high risk of developing metabolic disorders. Conclusion. In our study, an assessment of the impact of single nucleotide polymorphism of the CLOCK gene rs1801260 showed a high risk of developing a metabolically unhealthy obesity phenotype in carriers of the TC genotype: higher BMI (32.5 kg/m2), correlation with an increase in low-density lipoprotein levels cholesterol and a higher level of fasting glycemia. In the same group, patients noted a decrease in sleep quality and lack of vigor during the day (PSQI > 6).