Association of dopamine receptor polymorphisms with schizophrenia and antipsychotic response in a South Indian population.
BACKGROUND
Alterations in the dopamine transmission and receptor density are hypothesized in the pathophysiology of schizophrenia but ethnic disparities are reported to exist in disease association and therapeutic response to psychotropic medication. Antipsychotics have higher binding affinity to D2 subtype of dopamine receptor. DRD2 Cys311, TaqIB1 and TaqIA1 variants are considered to have either reduced affinity for dopamine and hypo-dopaminergic activity.


METHODS
We examined the role of Taq1B, Taq1D, S311C, H313H and Taq1A polymorphisms of DRD2 gene in schizophrenia and antipsychotic treatment response in 213 patients and 196 controls from a homogenous South Indian population. A more detailed genotype phenotype association analysis was carried out to understand the disease in terms of its socio-cultural factors.


RESULTS
H313HTT genotype was found to be associated with schizophrenia (P = 0.004) while TaqIB1B1 genotype was significantly associated with higher psychopathology score. When treatment response was considered H313HCC, TaqIA2A2 and Taq1D1D1 had higher mean improvement scores. TaqID1D1 and H313HTT genotype were found to be significantly higher in responders than in nonresponder group. Distinct shift in the LD patterns of responder and non-responder group was observed. Certain symptoms were characteristic of our patient population. Following medication the scores and presentation of these symptoms tend to vary in the responder and non-responder groups.


CONCLUSIONS
Based on genotype phenotype correlations it can be suggested that certain polymorphisms can be defined for their critical functions in disease and their role in treatment response in South Indian population. The present study suggests that in addition to ethnic bias, socio-cultural factors should also be considered while evaluating genotype phenotype correlations, in association and treatment response to complex disorders like schizophrenia.
Vijayan
Neetha N
NN
Human Molecular Genetics Laboratory, Rajiv Gandhi Centre for Biotechnology, Thiruvananthapuram, Kerala, India. neethav@yahoo.com
Bhaskaran
Sujatha
S
Koshy
Linda V
LV
Natarajan
Chandrasekhar
C
Srinivas
Lekshmy
L
Nair
Chandrasekharan M
CM
Allencherry
Priya M
PM
Banerjee
Moinak
M