Association of CCL11 promoter polymorphisms with schizophrenia in a Korean population

Abstract

BackgroundImmunological alterations and dysregulation of the inflammatory response have been suggested to play a crucial role in schizophrenia pathophysiology. Growing evidence supports the involvement of chemokines in brain development, thus many chemokines have been studied in relation with schizophrenia. The C-C motif chemokine ligand 11 (CCL11) has been shown to be related with synaptic plasticity and neurogenesis. Moreover, altered levels of CCL11 have been observed in schizophrenia patients. Therefore, we examined whether single nucleotide polymorphisms (SNPs) of the CCL11 in the promoter region contribute to susceptibility to schizophrenia. MethodsFour promoter SNPs [rs17809012 (-384T>C), rs16969415 (-426C>T), rs17735961 (-488C>A), and rs4795896 (576G>A)] were genotyped in 254 schizophrenia patients and 405 control subjects using Fluidigm SNPtype assays. ResultsThe genotype frequency of CCL11 rs4795896 (-576G>A) showed significant association with schizophrenia in a recessive model (AA vs. GG/AG, p < 0.0001) and in a log-additive model (AG vs. AA vs. GG, p < 0.0001). The allele frequency of rs4795896 also showed a significant association with schizophrenia (p < 0.0001). Furthermore, haplotype analysis revealed that GCT, ACT, and GCC haplotypes containing rs4795896, rs17735961 and rs17809012 were significantly associated with schizophrenia (p = 0.0044, p < 0.0001, and p < 0.0001, respectively). ConclusionOur results suggest that CCL11 promotor polymorphism is associated with increased risk for the development of schizophrenia in a Korean population.