Association between a casein kinase 1 ε gene polymorphism and schizophrenia in a Chinese Han population

Abstract

The casein kinase 1 (Csnk1) family of serine/threonine kinases regulates dopamine receptor (DR) signaling by phosphorylating the 32-kDa dopamine- and cAMP-regulated phosphoprotein DARPP-32, leading to inhibition of protein phosphatase 1 and a shift in the phosphorylation state of many downstream proteins. By modulating DR-activated phosphorylation cascades, Csnk1 plays a central role in neuropsychiatric disorders and modulates the stimulant response to amphetamine. No published study, however, has established a correlation between Csnk1 gene polymorphisms and schizophrenia. We genotyped the rs135745C/G polymorphism of the Csnk1ε gene in 384 schizophrenic patients and 502 healthy controls drawn from the Chinese Han population. There were significantly higher CG and CC genotype frequencies in schizophrenic patients compared to control subjects (CG, p = 0.0086, odds ratio (OR) = 1.477, 95% confidence interval (CI), 1.103-1.978; CC, p = 0.0431, OR = 2.571; 95% CI, 0.998-6.624). The C allele frequency was also higher in the schizophrenics (p = 0.0022; OR = 1.474; 95% CI, 1.149-1.891). In the dominant model, subjects with genotypes CC or CG were at greater risk for schizophrenia (p = 0.0032; OR = 1.532; 95% CI, 1.153-2.037), suggesting that a genetic variant in the Csnk1ε gene significantly enhances the probability of schizophrenia in the Chinese Han population.