PMID- 19207030
OWN - NLM
STAT- MEDLINE
DCOM- 20090518
LR  - 20090211
IS  - 1744-8042 (Electronic)
IS  - 1462-2416 (Linking)
VI  - 10
IP  - 2
DP  - 2009 Feb
TI  - Genetic susceptibility to schizophrenia: role of dopaminergic pathway gene 
      polymorphisms.
PG  - 277-91
LID - 10.2217/14622416.10.2.277 [doi]
AB  - AIM: We investigated 16 polymorphisms from three genes, dopamine receptor D2 
      (DRD2), catechol-O-methyl transferase (COMT) and brain derived neurotrophic 
      factor (BDNF), which are involved in the dopaminergic pathways, and have been 
      reported to be associated with susceptibility to schizophrenia and response to 
      antipsychotic therapy. MATERIALS & METHODS: Single-locus association analyses of 
      these polymorphisms were carried out in 254 patients with schizophrenia and 225 
      controls, all of southern Indian origin. Additionally, multifactor-dimensionality 
      reduction analysis was performed in 422 samples (243 cases and 179 controls) to 
      examine the gene-gene interactions and to identify combinations of multilocus 
      genotypes associated with either high or low risk for the disease. RESULTS: Our 
      results demonstrated initial significant associations of two SNPs for DRD2 
      (rs11608185, genotype: chi(2) = 6.29, p-value = 0.043; rs6275, genotype: chi(2) = 
      8.91, p-value = 0.011), and one SNP in the COMT gene (rs4680, genotype: chi(2) = 
      6.67, p-value = 0.035 and allele: chi(2) = 4.75, p-value = 0.029; odds ratio: 
      1.33, 95% confidence interval: 1.02-1.73), but not after correction for multiple 
      comparisons indicating a weak association of individual markers of DRD2 and COMT 
      with schizophrenia. Multifactor-dimensionality reduction analysis suggested a two 
      locus model (rs6275/DRD2 and rs4680/COMT) as the best model for gene-gene 
      interaction with 90% cross-validation consistency and 42.42% prediction error in 
      predicting disease risk among schizophrenia patients. CONCLUSION: The present 
      study thus emphasizes the need for multigene interaction studies in complex 
      disorders such as schizophrenia and to understand response to drug treatment, 
      which could lead to a targeted and more effective treatment.
FAU - Gupta, Meenal
AU  - Gupta M
AD  - Functional Genomics Unit, Institute of Genomics and Integrative Biology (Council 
      of Scientific and Industrial Research), Mall Road, Delhi 110 007, India.
FAU - Chauhan, Chitra
AU  - Chauhan C
FAU - Bhatnagar, Pallav
AU  - Bhatnagar P
FAU - Gupta, Simone
AU  - Gupta S
FAU - Grover, Sandeep
AU  - Grover S
FAU - Singh, Prashant K
AU  - Singh PK
FAU - Purushottam, Meera
AU  - Purushottam M
FAU - Mukherjee, Odity
AU  - Mukherjee O
FAU - Jain, Sanjeev
AU  - Jain S
FAU - Brahmachari, Samir K
AU  - Brahmachari SK
FAU - Kukreti, Ritushree
AU  - Kukreti R
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Pharmacogenomics
JT  - Pharmacogenomics
JID - 100897350
RN  - 0 (Brain-Derived Neurotrophic Factor)
RN  - 0 (DRD3 protein, human)
RN  - 0 (Receptors, Dopamine D3)
RN  - EC 2.1.1.6 (Catechol O-Methyltransferase)
SB  - IM
MH  - Adult
MH  - Amino Acid Substitution
MH  - Brain-Derived Neurotrophic Factor/*genetics
MH  - Case-Control Studies
MH  - Catechol O-Methyltransferase/*genetics
MH  - Exons
MH  - Female
MH  - *Genetic Predisposition to Disease
MH  - *Genetic Variation
MH  - Humans
MH  - India
MH  - Male
MH  - *Polymorphism, Genetic
MH  - *Polymorphism, Single Nucleotide
MH  - Receptors, Dopamine D3/*genetics
MH  - Reference Values
MH  - Schizophrenia/*genetics
MH  - Young Adult
EDAT- 2009/02/12 09:00
MHDA- 2009/05/19 09:00
CRDT- 2009/02/12 09:00
PHST- 2009/02/12 09:00 [entrez]
PHST- 2009/02/12 09:00 [pubmed]
PHST- 2009/05/19 09:00 [medline]
AID - 10.2217/14622416.10.2.277 [pii]
AID - 10.2217/14622416.10.2.277 [doi]
PST - ppublish
SO  - Pharmacogenomics. 2009 Feb;10(2):277-91. doi: 10.2217/14622416.10.2.277.