Association of BMAL1, CLOCK, and CRY1 gene polymorphisms with metabolic syndrome and glycemic phenotypes: a...

Metabolic syndrome (MetS) comprises cardiometabolic abnormalities that elevate the risk of type 2 diabetes and cardiovascular disease. Growing evidence links circadian rhythm disruption to obesity, diabetes, hypertension, and MetS. This study investigated functional polymorphisms in circadian rhythm-related genes and their associations with MetS and key clinical parameters. A total of 200 patients with MetS and 104 healthy controls were enrolled. Genotyping was performed using PCR-RFLP. Univariate and age-adjusted multivariable logistic regression analyses were conducted to evaluate independent genetic risk factors. The GC genotype of the CRY1 rs2287161 polymorphism was found to be significantly more frequent in the MetS group compared with healthy controls (p = 0.009). After adjusting for age in multivariable logistic regression, the CRY1 rs2287161 GC genotype remained a significant, independent factor for MetS ($\text{adjusted OR}=\text{0.381}$, $95\%\text{\hspace{0.17em} CI:\hspace{0.17em}}0.175-0.831$, $p=0.015$). No significant differences were observed between the MetS and control groups in terms of genotype distributions of BMAL1 rs7950226 and CLOCK rs1801260 (p > 0.05). Among MetS patients, individuals carrying the BMAL1 rs7950226 AA genotype exhibited significantly higher fasting plasma glucose levels compared with those carrying the GA and GG genotypes (p = 0.039). An altered distribution of the CRY1 rs2287161 polymorphism was observed in this Turkish cohort, with the GC genotype showing an age-independent statistical association with MetS risk. Additionally, BMAL1 rs7950226 variation modulates glycemic parameters within MetS patients, reinforcing the role of core circadian genes in metabolic regulation.