Association Between Tryptophan Hydroxylase-2 Gene and Late-Onset Depression Patricia de Ara ´ ujo Pereira, M.Sc., Marco Aur´ elio Romano-Silva, M.D., Ph.D., Maria Aparecida Camargos Bicalho, M.D., Ph.D., Luiz De Marco, M.D., Ph.D., Humberto Correa, M.D., Ph.D., Simone Becho de Campos, M.Sc., Edgar Nunes de Moraes, M.D., Ph.D., Karen Cecilia de Lima Torres, Ph.D., Bruno Rezende de Souza, Ph.D., Debora Marques de Miranda, M.D., Ph.D. Objective: The aim of this study was to examine the association between polymor- phisms (SNP) in the tryptophan hydroxylase-2 (TPH2) gene and late-onset depression (LOD) in the Brazilian population. Methods: We genotyped 8 tag SNPs in the TPH2 gene in 84 outpatients with LOD and 79 individuals belonging to the comparison group to investigate an association between the TPH2 gene and LOD. Results: Our findings suggested an association between tag SNP rs4565946 heterozygous C/T (p = 0.034; χ 2 = 6.7; df = 2) and decreased risk of LOD. The tag SNP rs11179000 ancestral homozygous A/A (p = 0.025; χ 2 = 7.3; df = 2) and increase risk of LOD and allelic association of ancestral allele A and increase risk of LOD was demonstrated (p = 0.005; χ 2 = 7.8; df = 1). Conclusion: We found the statistically significant associa- tion between two tag SNPs and LOD. Our results support the hypothesis that the TPH2 gene is associated with LOD. (Am J Geriatr Psychiatry 2011; 00:1–5) Key Words: Tryptophan hydroxylase-2 (TPH2), single-nucleotide polymorphism (SNP), late-onset depression (LOD). S erotonin is one of the main neurotransmitters of the central nervous system, and its role in psy- chiatric disorders is well recognized. 1 Tryptophan hydroxylase-2 (TPH2) is the rate-limiting enzyme in the synthetic pathway for brain serotonin 2 and is con- sidered key for maintaining normal serotonin trans- Received March 25, 2010; revised October 27, 2010; accepted December 10, 2010. From the Laborat´ orio de Neurociˆ encia, INCT—Instituto Nacional de Ciˆ encia e Tecnologia de Medicina Molecular, Faculdade de Medicina, Departamento de Sa´ ude Mental, Universidade Federal de Minas Gerais (UFMG), Av Alfredo Balena, 190, Belo Horizonte-MG, 30130, Brazil (PAP,MARS, MACB, LDM, HC, SBC, KCLT, BRS, DMM); Centro de Referˆ encia do Idoso, Hospital das Cl´ ınicas, Universidade Federal de Minas Gerais (UFMG), Brazil (MACB, ENM). This work was supported by CNPq, FAPEMIG and FINEP, INCT de Medicina Molecular; MAR-S was recipient of a J.S. Guggenheim Fellowship during the development of this study. Send correspondence and reprint requests to Patricia de Ara´ ujo Pereira M.Sc., the Laborat´ orio de Neurociˆ encia, INCT—Instituto Nacional de Ciˆ encia e Tecnologia de Medicina Molecular, Faculdade de Medicina. e-mail patriciabiomol@yahoo.com.br c  2011 American Association for Geriatric Psychiatry DOI: 10.1097/JGP.0b013e31820eeb21 mission in the CNS. 3 TPH2 single-nucleotide poly- morphisms (SNPs) are associated with many psychi- atric disorders, including major depression. 4 Major depression is the most common psychiatric disorder worldwide and its lifetime prevalence is high in the elderly. 5 One percent to 4% elderly present Copyright © Lippincott Williams & Wilkins. Unauthorized reproduction of this article is prohibited. Am J Geriatr Psychiatry 00:0, 00 2011 1