TY - JOUR
T1 - Brain-derived neurotrophic factor gene polymorphisms
T2 - Influence on treatment response phenotypes of major depressive disorder
AU - Kocabas, Neslihan Aygun
AU - Antonijevic, Irina
AU - Faghel, Carole
AU - Forray, Carlos
AU - Kasper, Siegfried
AU - Lecrubier, Yves
AU - Linotte, Sylvie
AU - Massat, Isabelle
AU - Mendlewicz, Julien
AU - Noro, Magali
AU - Montgomery, Stuart
AU - Oswald, Pierre
AU - Snyder, Lenore
AU - Zohar, Joseph
AU - Souery, Daniel
PY - 2011/1
Y1 - 2011/1
N2 - Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor family of neurotrophins, has pivotal roles in neuronal survival, proliferation, and synaptic plasticity in the brain. Both clinical and pharmacological studies have implicated the common single nucleotide polymorphism (SNP) at position 196, Val66Met in the pathophysiology of major depressive disorder (MDD), and antidepressant response. However, inconsistent results were found between Val66Met (rs6265) polymorphism and treatment response phenotypes in genetic association studies. The functional Val66Met polymorphism and seven other tagging SNP markers selected to capture the major allelic variations across BDNF locus were analyzed in depressed patients, treated with antidepressants, and 76 control patients. Two hundred and six patients with Diagnostic and Statistical Manual of Mental Disorders-IV MDD were recruited for this study and genotyped for eight BDNF tagging SNPs (rs11030096, rs925946, rs10501087, rs6265, rs12273363, rs908867, rs1491850, and rs1491851) to investigate the functional impact of genotypes/haplotypes in the susceptibility of depression and on treatment response. None of the eight SNPs, including the rs6265, were significantly associated with MDD after permutation correction. However, we found an association for rs10501087, rs6265 with nonresponse to antidepressant treatment (corrected permutation P: 0.03599; 0.0399 and power: 0.1420; 0.1492, respectively). Analysis of each two-marker, three-marker, and four-marker sliding window haplotypes showed significance in haplotype combinations. Especially rs10501087 (C), rs6265 (A), and rs1491850 (C) together or with the other SNP haplotypes showed a similar pattern in all treatment response phenotypes. Despite the limited power of analysis, our results suggest that these three SNPs may play a role in antidepressant treatment response phenotypes in MDD.
AB - Brain-derived neurotrophic factor (BDNF), a member of the nerve growth factor family of neurotrophins, has pivotal roles in neuronal survival, proliferation, and synaptic plasticity in the brain. Both clinical and pharmacological studies have implicated the common single nucleotide polymorphism (SNP) at position 196, Val66Met in the pathophysiology of major depressive disorder (MDD), and antidepressant response. However, inconsistent results were found between Val66Met (rs6265) polymorphism and treatment response phenotypes in genetic association studies. The functional Val66Met polymorphism and seven other tagging SNP markers selected to capture the major allelic variations across BDNF locus were analyzed in depressed patients, treated with antidepressants, and 76 control patients. Two hundred and six patients with Diagnostic and Statistical Manual of Mental Disorders-IV MDD were recruited for this study and genotyped for eight BDNF tagging SNPs (rs11030096, rs925946, rs10501087, rs6265, rs12273363, rs908867, rs1491850, and rs1491851) to investigate the functional impact of genotypes/haplotypes in the susceptibility of depression and on treatment response. None of the eight SNPs, including the rs6265, were significantly associated with MDD after permutation correction. However, we found an association for rs10501087, rs6265 with nonresponse to antidepressant treatment (corrected permutation P: 0.03599; 0.0399 and power: 0.1420; 0.1492, respectively). Analysis of each two-marker, three-marker, and four-marker sliding window haplotypes showed significance in haplotype combinations. Especially rs10501087 (C), rs6265 (A), and rs1491850 (C) together or with the other SNP haplotypes showed a similar pattern in all treatment response phenotypes. Despite the limited power of analysis, our results suggest that these three SNPs may play a role in antidepressant treatment response phenotypes in MDD.
KW - antidepressant
KW - brain-derived neurotrophic factor
KW - haplotype
KW - major depressive disorder
KW - tagging SNPs
KW - treatment response phenotype
UR - http://www.scopus.com/inward/record.url?scp=78650814423&partnerID=8YFLogxK
U2 - 10.1097/YIC.0b013e32833d18f8
DO - 10.1097/YIC.0b013e32833d18f8
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AN - SCOPUS:78650814423
SN - 0268-1315
VL - 26
SP - 1
EP - 10
JO - International Clinical Psychopharmacology
JF - International Clinical Psychopharmacology
IS - 1
ER -