BDNF rs6265 polymorphisms are associated with lower risk of type 2 diabetes: Gene‐nutrient interactions in the Korean Genome and Epidemiology Study
Authors: Park Sunmin , Daily James W. 
Published: November 2023

Brain‐derived neurotrophic factor (BDNF) plays a key role in regulating survival, growth and maintenance of neurons. It is associated with the risk of Alzheimer's disease and type 2 diabetes. The purpose of this study was to examine the association of BDNF variants with type 2 diabetes and the interactions of different BDNF genotypes with dietary habits and food and nutrient intakes in Korean adults. The analysis used data from the Korean Genome Epidemiology Study, a cross‐sectional study of Korean adults, conducted from 2001 to 2002. The study population included 8,840 adults aged 40–65 years from the Ansan and Asung areas in Korea. Adjusted odd ratios for the prevalence of type 2 diabetes according to BDNF genotypes were calculated after adjusting for age, gender, residence area, body mass index (BMI), and smoking and stress status. The interactions of dietary habits and BDNF genotypes and their assoications with type 2 diabetes were determined. The number of subjects of non‐diabetes, glucose intolerance and type 2 diabetes were 5,913, 1,931, and 998, respectively. BDNF rs6265 Val/Met and Met/Met variants were negatively associated with type 2 diabetic status after adjusting for covariates. Serum glucose levels during OGTT and HbA1C, but not serum insulin levels, were also negatively associated with BDNF Val/Met and Met/Met. In sub‐group analysis, males with BDNF Val/Met but females with BDNF Met/Met were negatively associated with diabetic status. The association of BDNF Val/Met and Met/Met with type 2 diabetes remained in the normal‐weight subgroup, however, there was no association in the obesity sub‐group. After adjusting for covariates, there was a significant association of BDNF Val/Met and Met/Met with diabetic status only in the regular exercise group. Only in no‐stress subgroup BDNF Val/Met remained as associated with diabetic status. In the smoking group BDNF Val/Met was negatively associated with diabetic status. Diabetic, but not non‐diabetic, subjects with BNDF Met/Met had higher intakes of energy and correspondingly higher intakes of many individual nutrients than those with BDNF Val/Val in 24‐h recall. Food frequency data revealed that BDNF variants were not significantly different for any food group in the non‐diabetic subjects, whereas in diabetic subjects the ORs for subjects with BDNF Val/Met food intakes were significantly higher for grains and rice+grains, and in subjects with BDNF Met/Met intakes were higher for grains, rice+grains, noodles, and milk product in comparison to those with BDNF Val/Val. However, fatty food, processed food groups and fruits showed no differences in ORs for BDNF genotypes. In conclusions, BDNF Val/Met and Met/Met variants (rs6265) may decrease the risk of type 2 diabetes and may provide some protection against dietary and lifestyle risk factors that increase the risk of type 2 diabetes.Support or Funding InformationFunding from the Korean Research Foundation (NRF‐2015R1D1A3A01019577).

Adjusted odds ratio for BDNF variants (rs6265) for type 2 diabetes and HbA1c levels after adjusting for covariates of age, gender, residence area (Model 1) and of age, gender, residence area, BMI, and smoking and stress status (Model 2).

Model 1
Model 2

Val/Val (n=2686)
Val/Met (n=4406)
Met/Met (1750)
Val/Met (n=4406)
Met/Met (n=4406)

Type diabetes
2
1
0.894 (0.833~0.960)**
0.932 (0.853~1.019)
0.884 (0.815~0.958)**
0.891 (0.804~0.987)*

HbAlc

1
0.950 (0.903~1.000)*
0.964 (0.904~1.027)
0.972 (0.915~1.031)
0.981 (0.910~1.057)

Glucose min
0
1
0.997 (0.995~1.000)*
1.000 (0.997~1.002)
0.998 (0.995~1.000)
1.000 (0.997~1.003)

Glucose min
60
1
0.998 (0.997~0.999)***
0.999 (0.998~1.000)
0.998 (0.997~0.999)***
0.999 (0.998~1.001)

Glucose min
120
1
0.998 (0.997~0.999)**
1.000 (0.992~1.007)
0.998 (0.997~0.999)**
0.999 (0.998~1.001)