Dopaminergic gene polymorphisms and cognitive function in a north Indian schizophrenia cohort.
BACKGROUND
Associations of polymorphisms from dopaminergic neurotransmitter pathway genes have mostly been reported in Caucasian ancestry schizophrenia (SZ) samples. As studies investigating single SNPs with SZ have been inconsistent, more detailed analyses utilizing multiple SNPs with the diagnostic phenotype as well as cognitive function may be more informative. Therefore, these analyses were conducted in a north Indian sample.


METHODS
Indian SZ case-parent trios (n = 601 families); unscreened controls (n = 468) and an independent set of 118 trio families were analyzed. Representative SNPs in the Dopamine D3 receptor (DRD3), dopamine transporter (SLC6A3), vesicular monoamine transporter 2 (SLC18A2), catechol-o-methyltransferase (COMT) and dopamine beta-hydroxylase (DBH) were genotyped using SNaPshot/SNPlex assays (n = 59 SNPs). The Trail Making Test (TMT) was administered to a subset of the sample (n = 260 cases and n = 302 parents).


RESULTS
Eight SNPs were nominally associated with SZ in either case-control or family based analyses (p < 0.05, rs7631540 and rs2046496 in DRD3; rs363399 and rs10082463 in SLC18A2; rs4680, rs4646315 and rs9332377 in COMT). rs6271 at DBH was associated in both analyses. Haplotypes of DRD3 SNPs incorporating rs7631540-rs2134655-rs3773678-rs324030-rs6280-rs905568 showed suggestive associations in both case-parent and trio samples. At SLC18A2, rs10082463 was nominally associated with psychomotor performance and rs363285 with executive functions using the TMT but did not withstand multiple corrections.


CONCLUSIONS
Suggestive associations with dopaminergic genes were detected in this study, but convincing links between dopaminergic polymorphisms and SZ or cognitive function were not observed.
Department of Genetics, University of Delhi South Campus, Benito Juarez Road, New Delhi 110 021, India; C. B. Patel Research Centre, Vile Parle (West), Mumbai, India. Electronic address: prachi_7@yahoo.com.
Prachi
P
Kukshal
Venkat Chowdari
VC
Kodavali
Vibhuti
V
Srivastava
Joel
J
Wood
Lora
L
McClain
Triptish
T
Bhatia
A M
AM
Bhagwat
Smita Neelkanth
SN
Deshpande
Vishwajit Laxmikant
VL
Nimgaonkar
B K
BK
Thelma
D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics; D003072:Cognition Disorders / Q000175:diagnosis / Q000209:etiology*; D015331:Cohort Studies; D050483:Dopamine Plasma Membrane Transport Proteins / Q000235:genetics*; D005192:Family Health; D005260:Female; D056726:Genetic Association Studies; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India; D015810:Linkage Disequilibrium; D008297:Male; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D050637:Receptors, Dopamine D3 / Q000235:genetics*; D012559:Schizophrenia / Q000150:complications* / Q000235:genetics*; D050493:Vesicular Monoamine Transport Proteins / Q000235:genetics
C493593:DRD3 protein, human; D050483:Dopamine Plasma Membrane Transport Proteins; D050637:Receptors, Dopamine D3; C493452:SLC18A2 protein, human; C493214:SLC6A3 protein, human; D050493:Vesicular Monoamine Transport Proteins; D002394:Catechol O-Methyltransferase
Association; Cognition; Dopamine genes; Haplotypes; SNPs; Schizophrenia