Association of dopamine receptor polymorphisms with schizophrenia and antipsychotic response in a South Indian population

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>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.</p> <p>Conclusion</p> <p>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.</p

Contribution from MHC-Mediated Risk in Schizophrenia Can Reflect a More Ethnic-Specific Genetic and Comorbid Background

The immune system seems to play a significant role in the development of schizophrenia. This becomes more evident with the emerging role of MHC complex and cytokines in schizophrenia. In the recent past, several GWAS have implied that the 6p21 region was associated with schizophrenia. However, the majority of these studies were performed in European populations. Considering tremendous variations in this region and the probability of South Indian populations being quite different from the European gene-pool from an immunogenetic point, the present study was initiated to screen SNPs in the 2.28 MB region, spanning the extended MHC locus, in 492 cases and controls from a South Indian population. We found a very strong association of rs3815087 with schizophrenia at both allelic and genotypic levels with a 7.3-fold increased risk in the recessive model. Interestingly, the association of none of the earlier reported GWAS hits, such as rs3130375, rs3131296, rs9272219, or rs3130297 were found to be replicable in our study population. rs3815087 lies in the 5&prime;UTR region of the psoriasis susceptibility 1 candidate 1 (PSORS1C1) gene, which further suggests that inflammatory processes might be an important common pathogenic pathway leading to both schizophrenia and psoriasis. The study hints at ethnic specific gene&ndash;environment interaction in determining the critical threshold for disease initiation and progression

Additional file 3: Figure S2. of Pro-inflammatory cytokines and their epistatic interactions in genetic susceptibility to schizophrenia

Meta-analysis of TNFA rs361525 risk allele A versus G allele in schizophrenia patients in comparison to Normal control using fixed and random model. (TIF 354 kb

Additional file 1: Table S1. of Pro-inflammatory cytokines and their epistatic interactions in genetic susceptibility to schizophrenia

In silico functional prediction of relevant SNPs in this study using F-SNP program. Table S2. PCR conditions and polymorphism detection through RFLP for cytokine gene polymorphism. Table S3. List of studies included in meta-analysis. Table S4. Genotype and allele frequencies of polymorphisms that show lack of association with schizophrenia. (DOCX 41 kb

Severity of symptoms based on initial BPRS score compared with the BPRS score after one year follow up of medication in responder and non responder patients

<p><b>Copyright information:</b></p><p>Taken from "Association of dopamine receptor polymorphisms with schizophrenia and antipsychotic response in a South Indian population"</p><p>http://www.behavioralandbrainfunctions.com/content/3/1/34</p><p>Behavioral and brain functions : BBF 2007;3():34-34.</p><p>Published online 25 Jul 2007</p><p>PMCID:PMC1947997.</p><p></p