Association between Interleukin 31 Receptor A Gene Polymorphism and Schizophrenia in Korean Population

Abstract

Recently, Sun et al (2008) reported that the IL6R polymorphism is associated with schizophrenia. Therefore, to detect the association between polymorphisms of interleukin 31 receptor A (IL31RA) and schizophrenia, we genotyped 9 SNPs [rs9292101 (intron 1), rs1009639 (exon 2, Pro43Pro), rs2161582 (intron 2), rs68761890 (intron 5), rs16884629 (intron 6), rs11956465 (intron 12), rs12153724 (intron 12), and rs16884641 (intron 14)] using the Golden Gate assay on Illumina BeadStation 500 GX. Two hundred eighteen patients with schizophrenia and 379 normal subjects were recruited. Patients with schizophrenia were diagnosed according to DSM-IV, and control subjects without history of psychiatric disorders were selected. We used SNPStats, Haploview, HapAnalyzer, SNPAnalyzer, and Helixtree programs for the evaluation of genetic data. Of nine polymorphisms, three SNPs (rs9292101, rs1009639, and rs11956465) were associated with schizophrenia. The rs9292101 and rs11956465 showed significant associations with the risk of schizophrenia in the codominant [rs9292101, odds ratio (OR)=0.74, 95% confidence interval (CI)=0.58~0.95, p=0.017] and recessive (rs11956465, OR=0.64, 95% CI=0.42~0.96, p=0.034) models, respectively. The rs1009639 also was statistically related to schizophrenia in both codominant (OR=0.76, 95% CI=0.60~0.97, p=0.025) and dominant (OR=0.66, 95% CI=0.44~0.98, p=0.035) models. Two linkage disequilibrium (LD) blocks were made. In the analysis of haplotypes, a haplotype (GCT) in block 1 and a haplotype (CCACAG) in block 2 showed significant associations between schizophrenia and control groups (haplotype GCT, frequency=0.509, chi square=4.199, p=0.040; haplotype CCACAG, frequency=0.289, chi square=5.691, p=0.017). The results suggest that IL31RA may be associated with risk of schizophrenia in Korean population.

Keywords: Haplotype; Interleukin 31 receptor A; Linkage disequilibrium; Schizophrenia; Single nucleotide polymorphism.

Fig. 1

Gene map and linkage disequilibrium (LD) in interleukin 31 receptor A (IL31RA) gene. (A) Gene map of single nucleotide polymorphisms (SNPs) in IL31RA. Exons are marked with box. The coding region is black-boxed and untranslated regions are white-boxed. Asterisk (*) indicates a significant SNP. Arrow indicates the location of each SNP. (B) LD coefficient (│D'│) and LD blocks among SNPs of IL31RA. Block 1 consists of rs9292101, rs1009639, and rs2161582. Block 2 comprises rs6873519, rs6861890, rs16884629, rs11956465, rs12153724, and rs16884641.