title: Folate metabolism genes, dietary folate and response to antidepressant medications in late-life depression.
abstract: OBJECTIVE
  The primary aims of this study were to (i) determine whether folate metabolism genetic polymorphisms predict age of onset and occurrence of late life depression; and (ii) determine whether folate metabolism genetic polymorphisms predict response to antidepressant medications in late-life depression.
  
  
  METHODS
  This study used the Conte Center for the Neuroscience of Depression and the Neurocognitive Outcomes of Depression in the Elderly Study database, which includes individuals aged ≥60. The folate nutrition assessment was determined by the Block Food Frequency Questionnaire. Genotype was evaluated for 15 single nucleotide polymorphisms from 10 folate metabolism genes. Logistic regression models were used to examine genetic polymorphisms and folate estimates with association with depression age of onset and remission status.
  
  
  RESULTS
  There were 304 Caucasians in the database, 106 of these were not depressed and 198 had a diagnosis of depression. There were no significant differences between remitters and non-remitters in age, sex or estimated folate intakes. There were no folate estimates or folate metabolism gene single nucleotide polymorphisms that significantly predicted age of onset of depression or occurrence of depression. Methionine synthase reductase (MTRR) A66G (rs1801394) was significantly associated with remission status (p = 0.0077) such that those with the AA genotype were 3.2 times as likely as those with the GG genotype to be in remission (p = 0.0020). Methylenetetrahydrofolate reductase A1298C (rs1801131) achieved a borderline significance for association with remission status (p = 0.0313).
  
  
  CONCLUSIONS
  The major finding from this study is that the MTRR A66G genotype predicts response to selective serotonin reuptake inhibitor antidepressants in late life depression.
authors.affiliation: Department of Clinical Research, Campbell University College of Pharmacy and Health Sciences, Buies Creek, NC, USA. jamerson@campbell.edu
authors.forename: Brenda D
authors.initials: BD
authors.lastname: Jamerson
authors.forename: Martha E
authors.initials: ME
authors.lastname: Payne
authors.forename: Melanie E
authors.initials: ME
authors.lastname: Garrett
authors.forename: Allison E
authors.initials: AE
authors.lastname: Ashley-Koch
authors.forename: Marcy C
authors.initials: MC
authors.lastname: Speer
authors.forename: David C
authors.initials: DC
authors.lastname: Steffens
mesh_terms: D017668:Age of Onset; D000368:Aged; D000928:Antidepressive Agents / Q000627:therapeutic use*; D003541:Cystathionine beta-Synthase / Q000235:genetics; D003866:Depressive Disorder / Q000188:drug therapy / Q000235:genetics; D004032:Diet; D005260:Female; D005287:Ferredoxin-NADP Reductase / Q000235:genetics; D005492:Folic Acid / Q000008:administration & dosage / Q000235:genetics / Q000378:metabolism*; D020022:Genetic Predisposition to Disease; D005838:Genotype; D012696:Glycine Hydroxymethyltransferase / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics; D011237:Predictive Value of Tests; D017367:Selective Serotonin Reuptake Inhibitors / Q000627:therapeutic use*
chemical_list: D000928:Antidepressive Agents; D003541:Cystathionine beta-Synthase; D005287:Ferredoxin-NADP Reductase; D005492:Folic Acid; D012696:Glycine Hydroxymethyltransferase; D042965:Methylenetetrahydrofolate Reductase (NADPH2); D017367:Selective Serotonin Reuptake Inhibitors; C111241:methionine synthase reductase; C520541:SHMT protein, human
keywords: antidepressants; depression; depressive disorder/genetics; folate; late-life depression; single nucleotide polymorphisms