title: Common genetic polymorphisms in the ABCB1 gene are associated with risk of major depressive disorder in male Portuguese individuals.
abstract: Major depressive disorder (MDD) is a highly prevalent disorder, which has been associated with an abnormal response of the hypothalamus-pituitary-adrenal (HPA) axis. Reports have argued that an abnormal HPA axis response can be due to an altered P-Glycoprotein (P-GP) function. This argument suggests that genetic polymorphisms in ABCB1 may have an effect on the HPA axis activity; however, it is still not clear if this influences the risk of MDD. Our study aims to evaluate the effect of ABCB1 C1236T, G2677TA and C3435T genetic polymorphisms on MDD risk in a subset of Portuguese patients. DNA samples from 80 MDD patients and 160 control subjects were genotyped using TaqMan SNP Genotyping assays. A significant protection for MDD males carrying the T allele was observed (C1236T: odds ratio (OR)=0.360, 95% confidence interval [CI]: [0.140-0.950], p=0.022; C3435T: OR=0.306, 95% CI: [0.096-0.980], p=0.042; and G2677TA: OR=0.300, 95% CI: [0.100-0.870], p=0.013). Male Portuguese individuals carrying the 1236T/2677T/3435T haplotype had nearly 70% less risk of developing MDD (OR=0.313, 95% CI: [0.118-0.832], p=0.016, FDR p=0.032). No significant differences were observed regarding the overall subjects. Our results suggest that genetic variability of the ABCB1 is associated with MDD development in male Portuguese patients. To the best of our knowledge, this is the first report in Caucasian samples to analyze the effect of these ABCB1 genetic polymorphisms on MDD risk.
authors.affiliation: 1 Molecular Oncology Group, IPO-Porto Research Center (CI-IPOP), Portuguese Institute of Oncology , Porto, Porto, Portugal .
authors.forename: Marlene
authors.initials: M
authors.lastname: Santos
authors.forename: Serafim
authors.initials: S
authors.lastname: Carvalho
authors.forename: Luís
authors.initials: L
authors.lastname: Lima
authors.forename: Augusto
authors.initials: A
authors.lastname: Nogueira
authors.forename: Joana
authors.initials: J
authors.lastname: Assis
authors.forename: Jorge
authors.initials: J
authors.lastname: Mota-Pereira
authors.forename: Paulo
authors.initials: P
authors.lastname: Pimentel
authors.forename: Dulce
authors.initials: D
authors.lastname: Maia
authors.forename: Diana
authors.initials: D
authors.lastname: Correia
authors.forename: Sofia
authors.initials: S
authors.lastname: Gomes
authors.forename: Agostinho
authors.initials: A
authors.lastname: Cruz
authors.forename: Rui
authors.initials: R
authors.lastname: Medeiros
mesh_terms: D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1 / Q000235:genetics*; D000293:Adolescent; D000328:Adult; D003865:Major Depressive Disorder / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011174:Portugal; D020133:Reverse Transcriptase Polymerase Chain Reaction; D055815:Young Adult
chemical_list: C513055:ABCB1 protein, human; D018435:ATP Binding Cassette Transporter, Subfamily B; D020168:ATP Binding Cassette Transporter, Subfamily B, Member 1