No association between the Val66Met polymorphism of the brain-derived neurotrophic factor gene and bipolar disorder in a Japanese population: a multicenter study

Background Two previous studies reported a significant association between a missense polymorphism (Val66Met) in the brain-derived neurotrophic factor (BDNF) gene and bipolar disorder; however, contradictory negative results have also been reported, necessitating further investigation. Methods We organized a multicenter study of a relatively large sample of 519 patients with bipolar disorder (according to DSM-IV criteria) and 588 control subjects matched for gender, age, and ethnicity (Japanese). Genotyping was done by polymerase chain reaction–based restriction fragment length polymorphism or direct sequencing. Results The genotype distributions and allele frequencies were similar among the patients and control subjects. Even if the possible relationships of the polymorphism with several clinical variables (i.e., bipolar I or II, presence of psychotic features, family history, and age of onset) were examined, no variable was related to the polymorphism. Conclusions The Val66Met polymorphism of the BDNF gene is unrelated to the development or clinical features of bipolar disorder, at least in a Japanese population.