Influence of CLOCK Gene Variants on Weight Response after Bariatric Surgery

Area of Science:

• Genetics
• Metabolic Health
• Bariatric Surgery Outcomes

Background:

• The Circadian Locomotor Output Cycles Kaput (CLOCK) gene plays a role in metabolic regulation.
• Previous research suggests a link between CLOCK gene variations and metabolic dysfunction, including obesity.
• Understanding genetic predispositions can inform personalized bariatric surgery strategies.

Purpose of the Study:

• To investigate the association between single nucleotide polymorphisms (SNPs) in the CLOCK gene and obesity.
• To analyze the relationship between CLOCK gene SNPs and long-term weight response following bariatric surgery (BS).
• To evaluate the influence of specific CLOCK gene variants on weight loss and regain after different BS techniques.

Main Methods:

• Case-control study involving 375 patients with morbid obesity (MO) and 230 controls.
• Genotyping of selected CLOCK gene SNPs using Taqman® probes and allelic discrimination.
• Statistical analysis using SNPStats, adjusting for clinical covariates and surgery type; linear regression for weight response at 6 years post-surgery.

Main Results:

• Two of three analyzed CLOCK gene SNPs were significantly associated with morbid obesity.
• The rs1801260 variant showed a protective effect against MO.
• The TT genotype of the rs3749474 variant demonstrated a strong association with MO (OR = 2.25, p = 0.0006).
• Both analyzed variants were significantly associated with long-term weight loss and weight regain after bariatric surgery, independent of pre-surgical factors.

Conclusions:

• Specific single nucleotide polymorphisms (SNPs) in the CLOCK gene are associated with morbid obesity.
• CLOCK gene variants influence the long-term efficacy of bariatric surgery in terms of weight management.
• These findings suggest CLOCK gene SNPs could serve as potential biomarkers for predicting obesity risk and bariatric surgery outcomes.