Dopaminergic Pathway Gene Polymorphisms and Genetic Susceptibility to Schizophrenia among North Indians

Abstract

OBJECTIVE: Understanding the etiology and pathogenesis of schizophrenia has been difficult due to the complex inheritance patterns, genetic heterogeneity and varied multiple nonlinear interactions between genes. Several lines of evidence indicate the involvement of neurotransmitter dopamine in the pathophysiology of this disorder. To analyze such a possible role of dopaminergic pathway gene polymorphisms, we used a case-control approach. METHOD: We genotyped a total of 31 potential single nucleotide polymorphism/variable number of tandem repeat markers from 9 candidate genes including the dopamine receptors and metabolizing enzymes (synthesis and degradation) in 215 schizophrenia cases and 215 healthy controls from North India. RESULTS: A nominally significant allelic association was observed in case of the catechol-O-methyltransferase rs362204 -/G (p = 0.028) marker whereas nominally significant genotypic associations were seen for tyrosine hydroxylase rs6356 A/G (p = 0.04) and dopamine beta-hydroxylase rs1108580 A/G (p = 0.025) following the case-control approach. Several significant haplotypic associations were observed from dopamine beta-hydroxylase, catechol-O-methyltransferase, and dopamine receptor D(2) genes. A significant interaction of tyrosine hydroxylase rs6356 A/G and catechol-O-methyltransferase rs362204 -/G markers was also observed following binary logistic regression analysis (p = 0.009). CONCLUSIONS: A contribution of dopaminergic pathway gene polymorphisms to schizophrenia seems possible in our sample set. However, considering the marginal levels of associations, interpopulation comparisons and replicate studies are warranted.