Aim Variations of dopamine receptor type 2 (DRD2) are among the key factors involved in the pathology of schizophrenia. Presence of certain SNPs in DRD2 gene also amend patients’ response to antipsychotics. Keeping in view the genetic diversity among populations and important role of DRD2 polymorphisms in schizophrenia, we aimed to study two of its SNPs rs1801028 and rs6277 in patients with schizophrenia from Pakistan. Methods A total of 100 schizophrenia cases and 100 healthy controls were recruited. DNA was extracted from whole blood followed by PCR, Sanger sequencing and genotyping of two SNPs, that is, rs1801028 and rs6277. Results No association of rs1801028 and rs6277 was found with schizophrenia in Pakistani population (P > .05). Highlight of our study is the association of polymorphism rs201256011 with schizophrenia (P = .001), which is being reported for the first time. Significant association of rs201256011 was also found with Positive and Negative Syndrome Scale negative, cognitive and total score (P < .05). Conclusion In conclusion, genetic variants rs1801028 and rs6277 of DRD2 are not associated with schizophrenia in Pakistani population. While, previously unreported polymorphism rs201256011 have shown significant association with schizophrenia and its severity. A large scale multicentre replication study is required to confirm the association of this SNP with schizophrenia.

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Background: Neurobiology of schizophrenia involves impairment of glutamatergic neurotransmission. In this context, polymorphism in glutamate Ionotropic receptor a-amino-3-hydroxy-5-methyl-4-propionic acid (AMPA) type subunit 1 encoded by Glutamate Ionotropic Receptor AMPA Type Subunit 1 Gene (GRIA), (rs1127386, G/A) can be considered as a substantial contributor in pathogenesis of schizophrenia. Therefore, a pilot study was planned to find out if the single nucleotide polymorphism of GRIA (rs1127386, G/A) is a risk factor for schizophrenia in the population of Pakistan. It maps at 5q33, a schizophrenia susceptible locus as per genome-wide association studies. Methodology: Following Diagnostic and Statistical Manual 5 (DSM 5) criteria guidelines, 50 schizophrenia cases were incorporated in this case-control study and 51 controls, individuals without any psychiatric illness. The sternness of illness was figured out using positive and negative syndrome scale score (PANSS) score. Genomic DNA was extracted from blood, and further analysis was done on gel electrophoresis after conducting ARMS (amplification refractory mutation system) PCR. Frequencies of reported genotype and allele within both groups were determined using the chi-square test. Results: Statistically significant difference was not found in genotype and allele frequencies of (rs1127386, G/A) (p>0.05) between cases and controls in the study population. The severity status of the disease was also independent of the polymorphism (p>0.05). Conclusion: This pilot study specifies that polymorphism rs1127386 is not a risk factor for schizophrenia, at least in the Pakistani population.