Brain-derived neurotrophic factor gene variants and obesity in former smokers

Objective: From genome-wide association studies, brain-derived neurotrophic factor (BDNF) locus on chromosome 11 was the only SNP associated with both smoking and body mass index (BMI). This study aims to explore the unique genetic predisposition to obesity in former smokers by examining the effects of BDNF on BMI and waist circumference (WC). Methods: We included 15,072 ethnic Chinese participants in the Guangzhou Biobank Cohort Study (GBCS) with data of four BDNF SNPs related to both body mass index (BMI) and smoking behavior. We used baseline smoke exposure data in 2003-2007 and follow-up outcomes of general obesity (by BMI) and central obesity (waist circumference) in 2008-2012. Odds ratios (ORs) and 95% confidence intervals (CIs) for general obesity and central obesity associated with these SNPs were derived from logistic regression. Results: Of 15,072 participants (3,169 men and 11,903 women), 1,664 (11.0%) had general and 7,868 (52.2%) had central obesity. We replicated the associations of the four BDNF SNPs with obesity and smoking status in the GBCS. In 1,233 former smokers, the rs6265 GG, versus AA, genotype was associated with higher risks of general obesity (OR=1.79, 95% CI=1.06-3.01) and central obesity (OR=2.08, 95% CI=1.47-2.92) after adjustment. These associations were not significant in never or current smokers. In former heavy (≥20 cigarettes/day) smokers, the rs6265 GG genotype showed a higher odds for general obesity (OR=2.15, 95% CI=1.05-4.40), while no association was found in former light (1-9 cigarettes/day) smokers. Similar results were found for the association of rs6265 with central obesity and for the associations of other two BDNF SNPs (rs4923457 and rs11030104) with both general and central obesity. Conclusions: We firstly identified the genetic predisposition (BDNF SNPs) to general and central obesity in former smokers, particularly in former heavy smokers. Funding Statement: This study was supported by research grants from the Guangdong Natural Science Foundation of China, Guangdong, China (Grant number: 9451062001003477); the Guangzhou Science and Information Bureau, Guangzhou, China (2012J5100041); the National Natural Science Foundation of China (81773502 and 81703308). The study is funded by The University of Hong Kong Foundation for Educational Development and Research, Hong Kong; the Guangzhou Public Health Bureau and the Guangzhou Science and Technology Bureau, Guangzhou, China; and The University of Birmingham, UK. Declaration of Interests: None declared. Ethics Approval Statement: The GBCS was approved by the Medical Ethics Committee of the Guangzhou Medical Association. All participants provided written informed consent before participating.