Drinking Habits and Physical Activity Interact and Attenuate Obesity Predisposition of TMEM18 Polymorphisms Carriers

The transmembrane protein 18 (TMEM18) gene plays a central and peripheral role in weight regulation. TMEM18 genetic polymorphisms have been identified as an important risk factor for obesity, depending on ethnic population and age. This research aimed to study the association of common TMEM18 polymorphisms with obesity and their interactions with modifiable factors, namely drinking habits (sugar-sweetened beverages (SSBs), flavored water and wine) and physical activity (PA) in the Israeli population. Adults (n = 3089) were analyzed for common TMEM18 polymorphisms and lifestyle and nutrition habits were obtained from questionnaires using adjusted (age, sex) binary logistic regression models. TMEM18 rs939583 and rs1879523 were significantly associated with increased obesity risk (OR = 1.35, 95% CI (1.17-1.57) and OR = 1.66, 95% CI (1.29-2.15), respectively). TMEM18 rs939583 interacted with consumption of 1-3 weekly glasses of wine and PA to attenuate obesity risk (OR = 0.82 95% CI (0.74-0.9; p < 0.001) and OR = 0.74 95% CI (0.68-0.8), respectively), while physical inactivity, SSBs and flavored water consumption significantly enhanced obesity risk (OR = 1.54 95% CI (1.41-1.67), OR = 1.31 95% CI (1.14-1.51) and OR = 1.35 95% CI (1.13-1.62), respectively). PA duration was significantly associated with a lower BMI for rs939583 risk carriers, with a PA cutoff of >30 min/week (p = 0.005) and >90 min/week (p = 0.01). Common TMEM18 SNPs were significantly linked with adult obesity risk and interacted with modifiable lifestyle factors.