Relationship between HECTD4 gene variants, obesity, and coffee consumption

In genome-wide association studies, the HECT domain E3 ubiquitin-protein ligase 4 (HECTD4) gene was suggested to be associated with obesity-related traits and coffee consumption. However, the association of genetic variants between coffee consumption and obesity has not been tested in Koreans. Therefore, we investigated whether HECTD4 gene variants act as effect modifiers on the relationship between obesity and coffee.

This study analyzed the correlation between coffee consumption and obesity among 58,698 individuals representing the Health Examinees. Participants were categorized into obese (BMI ≥ 25.0 kg/m²) and nonobese (18.5 ≤ BMI < 23.0 kg/m²). Food consumption was assessed by a food frequency questionnaire.

We identified four HECTD4 gene variants associated with obesity-related traits and coffee consumption based on Bonferroni-corrected significance level (p < 0.00014). Furthermore, multivariate logistic regression analysis confirmed that the impact of coffee consumption on obesity differed based on the HECTD4 rs2074356 genotypes. A positive correlation between obesity and coffee consumption was observed, with a more pronounced effect in individuals with the G allele (OR = 1.61 for 1 to <2 cups/day, p = 1.89 × 10⁻³⁷; OR = 1.82 for ≥2 cups/day, p = 1.73 × 10⁻⁴²) than in those with the A allele (OR = 1.47 for 1 to <2 cups/day, p = 7.41 × 10⁻¹⁷; OR = 1.45 for ≥2 cups/day, p = 7.24 × 10⁻¹¹).

Our findings suggest that the influence of coffee consumption on obesity may vary in Koreans depending on the HECTD4 gene variant.