Impact of Brain-Derived Neurotrophic Factor Val66Met Polymorphism on Cortical Thickness and Voxel-Based Morphometry in Healthy Chinese Young Adults

Xuejuan Yang,Minghao Dong,Fang Zeng,Kai Yuan,Wei Qin,Jie Tian,Jinbo Sun,Karen M Von Deneen,Jixin Liu,Guihong Wang,Peng Liu,Pedro Antonio Valdes-Sosa

doi:10.1371/journal.pone.0037777

Abstract

BackgroundFollowing voxel-based morphometry (VBM), brain-derived neurotrophic factor (BDNF) Val66Met polymorphism (rs6265) has been shown to affect human brain morphology in Caucasians. However, little is known about the specific role of the Met/Met genotype on brain structure. Moreover, the relationship between BDNF Val66Met polymorphism and Chinese brain morphology has not been studied.Methodology/Principal FindingsThe present study investigated brain structural differences among three genotypes of BDNF (rs6265) for the first time in healthy young Chinese adults via cortical thickness analysis and VBM. Brain differences in Met carriers using another grouping method (combining Val/Met and Met/Met genotypes into a group of Met carriers as in most previous studies) were also investigated using VBM. Dual-approach analysis revealed less gray matter (GM) in the frontal, temporal, cingulate and insular cortices in the Met/Met group compared with the Val/Val group (corrected, P<0.05). Areas with less GM in the Val/Met group were included in the Met/Met group. VBM differences in Met carriers were only found in the middle cingulate cortex.Conclusions/SignificanceThe current results indicated a unique pattern of brain morphologic differences caused by BDNF (rs6265) in young Chinese adults, in which the Met/Met genotype markedly affected the frontal, temporal, cingulate, and insular regions. The grouping method with Met carriers was not suitable to detect the genetic effect of BDNF Val66Met polymorphism on brain morphology, at least in the Chinese population, because it may hide some specific roles of Met/Met and Val/Met genotypes on brain structure.

Highlights

With the rise of imaging genomics, more and more studies have demonstrated that brain structure and function are under strong genetic control [1]
The Met/Met homozygotes and the Val/Met heterozygotes were often merged into a group of Met carriers for analyses in most of these studies, which undoubtedly limited the detection of the specific role of the Met/Met genotype on brain structure
Our negative results were consistent with several recent reports, in which no evidence for an influence of the brain-derived neurotrophic factor (BDNF) Val66Met genotype on magnetic resonance imaging (MRI)-derived reduced hippocampus volume was found [8,38,39,40]. One reason for these conflicting results may be due to the fact that our study focused on the Chinese population, unlike previous positive studies [6,7]; the genetic effect of BDNF Val66Met polymorphism on hippocampal morphology remains controversial and requires further investigation

Summary

Introduction

With the rise of imaging genomics, more and more studies have demonstrated that brain structure and function are under strong genetic control [1]. The Met allele carriers showed less gray matter (GM) volume in some brain areas, such as the hippocampus [6,7], subgenual anterior cingulated [8], dorsolateral prefrontal cortex (DLPFC) [7,9], amygdale [10], and temporal and occipital lobar regions [11], compared with Val/Val homozygotes. These previous studies have provided little information on individuals who are homozygous for the Met allele (Met/Met) because of its small frequency in Caucasians. The relationship between BDNF Val66Met polymorphism and Chinese brain morphology has not been studied

Methods

Results

Conclusion