Association study of BDNF Val66Met gene polymorphism with bipolar disorder and lithium treatment response in Indian population

Background The association of the Val66Met (rs6265) polymorphism in the brain derived neurotrophic factor ( BDNF ) gene with bipolar disorder (BD) and response to lithium treatment has been suggested, though inconsistently. The considerable diversity of allele frequency across different populations contributes to this. There is no data from South Asia till date. Hence, we examined the association of this polymorphism in BD cases from India, and its correlation with lithium treatment response. Methods BD patients (N=301) were recruited from the clinical services of National Institute of Mental Health and Neurosciences (NIMHANS), India. Lithium treatment response for 190 BD subjects was assessed using Alda scale by NIMH life charts. Patients with total score ≥ 7 were defined as lithium responders (N=115) and patients with score <7 were defined as lithium non-responders (N=75). Healthy controls (N = 484) with no lifetime history of neuropsychiatric illness, or a family history of mental illness were recruited as control set. Genotyping was performed by TaqMan genotyping assay. Results Genotype and allele frequency of BDNF Val66Met SNP was significantly different (χ2 = 7.78, p=0.02) in cases compared to controls, and the Val(G) allele was more frequent (χ2 = 7.08, p=0.008) in BD patients. Although there was trend towards significance for greater occurrence of Val(G) allele among lithium non-responders, this difference did not persist in an analysis of extreme response groups. Conclusions The Val(G) allele of BDNF Val66Met polymorphism is associated with risk of BD in this sample, but is not related to response to lithium.