Abstract:
Recently, the direct-to-consumer (DTC) genetic testing system has been implemented in Korea, allowing individuals to obtain genetic information for non-clinical purposes. Although genes such as FTO, MC4R, and BDNF have been approved as candidate obesity-related markers for increasing BMI in Korea, further scientific evidence is warranted. BDNF, which is highly expressed in the hypothalamus, plays a role in appetite suppression and energy expenditure through physical activity. The Val66Met polymorphism (rs6265) is known to be associated with disordered eating behaviors, leading not only to obesity but also to an increased risk of depression and Alzheimer’s disease. Among the total participants (n = 231), the minor allele frequency (MAF) of BDNF (rs6265) was 47.4%, which is approximately three times higher than that reported for Europeans (19.4%) and Americans (14.8%). The proportion of heterozygous and mutant genotypes (H+M) was significantly higher in the obese group compared to the wild-type (W) group. For this reason, BDNF was selected as a primary candidate gene for this study, instead of FTO or MC4R. Analysis of gene-obesity interactions showed that obese individuals carrying H+M exhibited lower resting metabolic rate per body weight (RMR/BW), higher waist-to-hip ratio (WHR), elevated blood liver damage markers (ALT/AST), HbA1c, total cholesterol (TC), and LDL cholesterol. Compared to W carriers, H+M carriers consumed more sodium and only about one-fourth the amount of polyunsaturated fatty acids (PUFA, particularly ω-3 and ω-6). Therefore, sodium reduction is essential for obese individuals with H+M genotypes. Risk factors for increased BMI and RMR included BDNF (H+M), male, lower age, higher WHR, elevated ALT, higher leptin, and lower HDLc. For WHR increase, significant factors were BDNF (H+M), female sex, lower RMR/BW, elevated ALT, and higher vitamin A intake. In conclusion, obese individuals carrying the H+M genotype should reduce sodium intake and increase the intake of essential fatty acids (ω-3 and ω-6) and vitamin A. In particular, obese men should also reduce alcohol consumption to maintain healthy liver and lipid profiles, thereby preventing obesity progression. Given that the MAF of BDNF in Asians (44.5%) is similar to that of Koreans, the findings of this study may be applicable to other Asian populations as well.
