title: Association analysis of the catechol-O-methyltransferase /methylenetetrahydrofolate reductase genes and cognition in late-onset depression.
abstract: OBJECTIVE
  Increasing evidence suggests that the catechol-O-methyltransferase (COMT) gene might be associated with cognition in patients with mental disorders and healthy people. The metabolic pathways of COMT and methylenetetrahydrofolate reductase (MTHFR) are closely interconnected. In this study, we aimed to examine whether the COMT-MTHFR genotype interacted with cognitive function in late-onset depression (LOD) patients and COMT Val/Val homozygous individuals who also carried the MTHFR T allele and had poor neuropsychological test performance.
  
  
  METHODS
  Ninety-seven unrelated LOD patients who met DSM-IV criteria for major depressive disorder were recruited for the study and 103 normal controls were recruited from the local community. All of these patients and 44 normal controls completed a series of neuropsychological tests. Patients and normal controls were genotyped for COMT (rs4680) and MTHFR (rs1801133) variants using polymerase chain reaction-restriction fragment length polymorphism.
  
  
  RESULTS
  There were no significant differences in the frequencies of the single alleles and genotypes of two polymorphisms between LOD patients and normal controls. No main effects of COMT or MTHFR genotype on any neuropsychological test performance were observed. There was a significant interactive effect of COMT Val158Met and MTHFR C677T polymorphisms on the Symbol Digit Modalities Test independent of diagnosis (P < 0.05). After controlling for covariates, the subjects with COMT Met/ Met and MTHFR C/C genotype had better Symbol Digit Modalities Test performance.
  
  
  CONCLUSIONS
  The results suggest no major effect of COMT or MTHFR on cognitive function alone. However, an interaction of COMT Val158Met and MTHFR C677T polymorphisms may be associated with cognitive function. Further studies in a large sample are needed to replicate the genetic role in the LOD patients.
authors.affiliation: Department of Psychiatry, The 4th People's Hospital of Wuhu City, Wuhu, China.
authors.forename: Xiaoquan
authors.initials: X
authors.lastname: Wang
authors.forename: Zusen
authors.initials: Z
authors.lastname: Wang
authors.forename: Yanfeng
authors.initials: Y
authors.lastname: Wu
authors.forename: Yonggui
authors.initials: Y
authors.lastname: Yuan
authors.forename: Zhenghua
authors.initials: Z
authors.lastname: Hou
authors.forename: Gang
authors.initials: G
authors.lastname: Hou
mesh_terms: D017668:Age of Onset; D000368:Aged; D000483:Alleles; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D003071:Cognition; D003865:Major Depressive Disorder / Q000453:epidemiology / Q000235:genetics* / Q000523:psychology*; D004843:Epistasis, Genetic / Q000235:genetics; D005260:Female; D005838:Genotype; D006801:Humans; D008297:Male; D042965:Methylenetetrahydrofolate Reductase (NADPH2) / Q000235:genetics*; D009483:Neuropsychological Tests; D020641:Polymorphism, Single Nucleotide / Q000235:genetics
chemical_list: C573423:MTHFR protein, human; D042965:Methylenetetrahydrofolate Reductase (NADPH2); C588010:COMT protein, human; D002394:Catechol O-Methyltransferase
keywords: catechol-O-methyltransferase; cognitive function; late-onset; major depressive disorder; methylenetetrahydrofolate reductase