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Ban, Kim, Kim, Chung, Kim, Park, Park, and Kim: Association between Interleukin 31 Receptor A Gene Polymorphism and Schizophrenia in Korean Population
Original Article

Korean J Physiol Pharmacol 2008;12(4):205-209.

Published online: 17 August 2008

DOI: https://doi.org/10.4196/kjpp.2008.12.4.205

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

Ju Yeon Ban1, ∗, Su Kang Kim1, ∗, Hak-Jae Kim1, Joo-Ho Chung1, Tae Kim2, Jin Kyung Park2, Hyun-Kyung Park1, 3, Jong Woo Kim2

1Kohwang Medical Research Institute, Kyung Hee University, Seoul 130-701, Korea

2Department of Neuropsychiatry, Kyung Hee University, Seoul 130-701, Korea

3Department of Emergency Medicine, School of Medicine, Kyung Hee University, Seoul 130-701, Korea

Corresponding to: Corresponding to: Jong Woo Kim, Department of Neuropsychiatry, School of Medicine, Kyung Hee University, 1, Hoegi-dong, Dongdaemun-gu, Seoul 130-701, Korea. (Tel) 82-2-958-8543, (Fax) 82-2-968-0560, (E-mail) psyjongwoo@freechal.com, psyjong@khmc.or.kr

∗ These first authors contributed equally to this article.

Copyright © 2008 Korean J Physiol Pharmacol

This is an Open Access article distributed under the terms of the Creative Commons Attribution Non-Commercial License (http://creativecommons.org/licenses/by-nc/3.0) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

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: Interleukin 31 receptor A, Haplotype, Linkage disequilibrium, Schizophrenia, Single nucleotide polymorphism

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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.
kjpp-12-205f1.tif
Table 1.
Logistic regression analysis and genotype frequency of interleukin 31 receptor A (IL31RA) polymorphisms in patients with schizophrenia and controls
SNP Genotype Schizophrenia Control Codominant p Dominant p Recessive p
Locus n=218 (%) n=379 (%) OR (95% CI) OR (95% CI) OR (95% CI)
rs9292101 G/G 49 (23.2) 110 (30.1) 0.74 (0.58~0.95) 0.017 0.68 (0.46~1.01) 0.053 0.67 (0.45~1.00) 0.051
Intron 1 G/T 105 (49.8) 182 (49.7)            
  T/T 57 (27.0) 74 (20.2)            
rs1009639 C/C 47 (21.8) 110 (29.1) 0.76 (0.60~0.97) 0.025 0.66 (0.44~0.98) 0.035 0.74 (0.50~1.08) 0.120
Exon 2 C/T 108 (50.0) 182 (48.1)            
(Pro43Pro) T/T 61 (28.2) 86 (22.8)            
rs2161582 T/T 56 (26.1) 108 (29.8) 0.82 (0.65~1.05) 0.120 0.81 (0.55~1.19) 0.290 0.73 (0.48~1.10) 0.140
Intron 2 C/T 107 (49.8) 185 (51.0)            
  C/C 52 (24.2) 70 (19.3)            
rs6873519 A/A 75 (34.6) 118 (31.1) 1.20 (0.94~1.53) 0.140 1.16 (0.81~1.65) 0.430 1.48 (0.94~2.35) 0.088
Intron 4 A/C 111 (51.1) 183 (48.3)            
  C/C 31 (14.3) 78 (20.6)            
rs6861890 C/C 73 (33.8) 154 (40.6) 0.80 (0.62~1.02) 0.076 0.74 (0.52~1.06) 0.095 0.75 (0.47~1.22) 0.250
Intron 5 C/T 109 (50.5) 176 (46.4)            
  T/T 34 (15.7) 49 (12.9)            
rs16884629 G/G 113 (53.3) 167 (47.4) 1.27 (0.95~1.70) 0.110 1.23 (0.87~1.73) 0.250 2.05 (0.86~4.86) 0.086
Intron 6 A/G 92 (43.4) 160 (45.5)            
  A/A 7 (3.3) 25 (7.1)            
rs11956465 C/C 46 (22.4) 96 (27.1) 0.78 (0.60~1.00) 0.052 0.81 (0.54~1.22) 0.300 0.64 (0.42~0.96) 0.034
Intron 12 C/T 105 (51.2) 192 (54.2)            
  T/T 54 (26.3) 66 (18.6)            
rs12153724 G/G 65 (30.5) 92 (25.6) 1.15 (0.89~1.47) 0.290 1.28 (0.88~1.88) 0.200 1.09 (0.71~1.67) 0.690
Intron 12 A/G 107 (50.2) 191 (53.1)            
  A/A 41 (19.2) 77 (21.4)            
rs16884641 T/T 63 (29.2) 92 (24.3) 1.20 (0.94~1.52) 0.140 1.28 (0.88~1.88) 0.200 1.26 (0.84~1.88) 0.270
Intron 14 G/T 108 (50.0) 190 (50.3)            
  G/G 45 (20.8) 96 (25.4)            

Genotype distributions are shown as number (%). Odds ratio (OR), 95% confidence interval (CI), and p-values were from logistic regression analysis with codominant, dominant, and recessive models controlling age and gender as covariates. Total number of each SNP is different, because genotypes of some SNPs are unreadable. SNP, single nucleotide polymorphism.

Table 2.
Haplotype analysis of interleukin 31 receptor A (IL31RA) polymorphisms in patients with schizophrenia and controls
Block   Haplotype Freq Schizophrenia Control Chi square p
+ − + −
Block 1 ht1 GCT 0.509 203.0 229.0 403.0 355.0 4.199 0.040
  ht2 TTC 0.451 210.9 221.1 325.9 432.1 3.773 0.052
Block 2 ht1 ATGTGT 0.368 172.3 261.7 265.9 490.1 2.423 0.120
  ht2 CCACAG 0.289 107.6 326.4 236.7 519.3 5.691 0.017
  ht3 ACGTGT 0.131 56.4 377.6 99.4 656.6 0.007 0.935
  ht4 CCGCAG 0.126 560.0 378.0 93.6 662.4 0.071 0.790

Each haplotype with a frequency of more than 0.1 is shown. p-values of haplotype association were calculated using Haploview 3.32. ht, haplotype; Freq, frequency.

Table 3.
Genotype frequencies of interleukin 31 receptor A (IL31RA) polymorphisms in each population
SNP Genotype Korean European Chinese Japanese
Schizophrenia Control
rs9292101 G/G 0.232 0.301 0.085 0.326 0.209
  G/T 0.498 0.497 0.424 0.512 0.581
  T/T 0.27 0.202 0.492 0.163 0.209
rs1009639 C/C 0.218 0.291 0.083 0.311 0.2
  C/T 0.500 0.481 0.450 0.533 0.6
  T/T 0.282 0.228 0.467 0.156 0.2
rs2161582 T/T 0.261 0.298 0.417 0.111 0.182
  C/T 0.498 0.510 0.467 0.556 0.614
  C/C 0.242 0.193 0.117 0.333 0.205
rs6873519 A/A 0.346 0.311 0.567 0.4 0.356
  A/C 0.511 0.483 0.35 0.422 0.467
  C/C 0.143 0.206 0.083 0.178 0.178
rs6861890 C/C 0.338 0.406 0.317 0.444 0.25
  C/T 0.505 0.464 0.483 0.444 0.523
  T/T 0.157 0.129 0.200 0.111 0.227
rs1688462 9 G/G 0.533 0.474 0.000 0.093 0.095
  A/G 0.434 0.455 1.000 0.395 0.452
  A/A 0.033 0.071 0.000 0.512 0.452
rs1195646 5 C/C 0.224 0.271 0.050 0.178 0.156
  C/T 0.512 0.542 0.317 0.511 0.511
  T/T 0.263 0.186 0.633 0.311 0.333
rs1215372 4 G/G 0.305 0.256 0.051 0.195 0.146
  A/G 0.502 0.531 0.339 0.512 0.512
  A/A 0.192 0.214 0.61 0.293 0.341
rs1688464 1 T/T 0.292 0.243 0.05 0.178 0.156
  G/T 0.500 0.503 0.333 0.511 0.511
  G/G 0.208 0.254 0.617 0.311 0.333

From SNP database (http://www.ncbi.nlm.nih.gov/sites/entrez).

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