Schizophrenia is a neuropsychiatric disorder in which abnormalities in the prefrontal cortex lead to impaired
synthesis of dopamine. It is associated with hallucination, psychosis and hearing impairments. Many susceptible genes
have been identified in schizophrenia such as catechol-O-methyltransferase (COMT) and serine/threonine kinase (AKT1).
Single nucleotide polymorphisms (SNPs) in these genes have not been identified in Pakistan. Therefore, we investigated
the allelic and genotypic frequencies in COMT and AKT1 genes in the Pakistani population. Polymerase chain reactionrestriction
fragment length polymorphism (PCR-RFLP) and DNA sequencing were used to identify SNPs in the genes.
The present study shows that COMT Val and COMT Met allelic frequencies for the controls were p=0.52, q=0.48 and for
the schizophrenic cases they were p=0.34, q=0.66 respectively. The distribution of polymorphism in COMT Val158Met
genotype by Hardy-Weinberg equilibrium (HWE) was P=0.61 for controls and P=0.005 for cases. The data reveal that
SNP rs1130214 T allele mutation was found neither in patients nor in controls in the 5’ untranslated region (UTR). This
proves that no association of AKT1 and positive association of COMT with schizophrenia exist in the population of
Pakistan. Moreover, a study based on a single family showed COMT Met allele inheritance in schizophrenic offspring.
This suggested that COMT allele alteration influences susceptibility to at least some forms of psychosis in the Pakistani
population. Interestingly, according to our socio-economical survey, COMT genotype has no association with cannabis
but it is strongly associated with tobacco. The Pakistani population with Val158Met SNP showed more susceptibility
towards developing schizophrenia. This study highlights the genetic differences between Pakistani and other Caucasian
Keywords: Catechol-O-methyltransferase, Hardy-Weinberg equilibrium, methionine, Pakistan, schizophrenia, serine-threonine
protein kinase, single nucleotide polymorphisms, valine.
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