title: Association of Single Nucleotide Polymorphisms in Catechol-O-Methyltransferase and Serine-Threonine Protein Kinase Genes in the Pakistani Schizophrenic Population: A Study with Special Emphasis on Cannabis and Smokeless Tobacco.
abstract: 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 populations.
authors: Rukhsana
authors: R
authors: Nawaz
authors: Department of Neuroscience, Dr. Panjwani Center for Molecular Medicine and Drug Research, International Center for Chemical and Biological Sciences, University of Karachi, Karachi 75270, Pakistan. siddisbs@yahoo.com.
authors: Sonia
authors: S
authors: Siddiqui
mesh_terms: D000293:Adolescent; D000328:Adult; D002188:Cannabis; D016022:Case-Control Studies; D002394:Catechol O-Methyltransferase / Q000235:genetics*; D002648:Child; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008385:Marijuana Smoking / Q000453:epidemiology / Q000235:genetics; D008875:Middle Aged; D010154:Pakistan / Q000453:epidemiology; D020641:Polymorphism, Single Nucleotide; D015995:Prevalence; D051057:Proto-Oncogene Proteins c-akt / Q000235:genetics*; D012559:Schizophrenia / Q000453:epidemiology / Q000235:genetics*; D019966:Substance-Related Disorders / Q000453:epidemiology / Q000235:genetics; D064424:Tobacco Use / Q000453:epidemiology / Q000235:genetics*; D014030:Tobacco, Smokeless; D055815:Young Adult
chemical_list: C588010:COMT protein, human; D002394:Catechol O-Methyltransferase; C494918:AKT1 protein, human; D051057:Proto-Oncogene Proteins c-akt