title: Variants in MHC, LCE and IL12B have epistatic effects on psoriasis risk in Chinese population.
abstract: BACKGROUND
  Psoriasis has long been considered as a complex disease, and gene-gene or gene-environment interactions may jointly influence the etiology for psoriasis.
  
  
  OBJECTIVE
  We evaluated the associations of single nucleotide polymorphisms (SNPs) in MHC region, and determined the epistasis and combined effects of MHC locus and IL12B, LCE on risk for psoriasis.
  
  
  METHODS
  We genotyped SNP rs1265181 (MHC) in 5067 cases and 6404 controls, combining with the prior GWAS data (1139 cases and 1132 controls), we explored the genetic interaction among MHC locus, LCE and IL12B by using logistic regression analysis. We evaluated the combined effects of MHC locus and two non-MHC loci in the combined sample of 6206 cases and 7536 controls.
  
  
  RESULTS
  Extremely high significance of association was detected between rs1265181 and psoriasis (p combined < 10E--300, OR = 16.52, 95% CI: 15.28-18.44). We observed significant interactions between MHC and LCE (p = 0.0016) and between MHC and IL12B (p = 0.0036). The risk increased some 26-fold in individuals with risk alleles in both MHC and LCE as compared with those without risk alleles, and individual carrying risk alleles of MHC and IL12B has around 36-fold higher risk of psoriasis than those with protective alleles.
  
  
  CONCLUSIONS
  This study provides evidence for the epistatic effects between MHC locus and LCE, IL12B genes. Besides, we suggest that MHC might be the main effect gene on the risk for psoriasis. This data may contribute to our understanding of psoriasis genetic interactions and account for the additional risk of certain patients to develop psoriasis.
authors.affiliation: Institute of Dermatology, Anhui Medical University, Hefei, Anhui 230022, China.
authors.forename: Hou-Feng
authors.initials: HF
authors.lastname: Zheng
authors.forename: Xian-Bo
authors.initials: XB
authors.lastname: Zuo
authors.forename: Wen-Sheng
authors.initials: WS
authors.lastname: Lu
authors.forename: Yang
authors.initials: Y
authors.lastname: Li
authors.forename: Hui
authors.initials: H
authors.lastname: Cheng
authors.forename: Kun-Ju
authors.initials: KJ
authors.lastname: Zhu
authors.forename: Xian-Yong
authors.initials: XY
authors.lastname: Yin
authors.forename: Chi
authors.initials: C
authors.lastname: Zhang
authors.forename: Yun-Qing
authors.initials: YQ
authors.lastname: Ren
authors.forename: Wen-Ju
authors.initials: WJ
authors.lastname: Wang
authors.forename: Liang-Dan
authors.initials: LD
authors.lastname: Sun
authors.forename: Yong
authors.initials: Y
authors.lastname: Cui
authors.forename: Sen
authors.initials: S
authors.lastname: Yang
authors.forename: Feng-Yu
authors.initials: FY
authors.lastname: Zhang
authors.forename: Xue-Jun
authors.initials: XJ
authors.lastname: Zhang
mesh_terms: D000328:Adult; D000483:Alleles; D016009:Chi-Square Distribution; D002648:Child; D002681:China; D055233:Cornified Envelope Proline-Rich Proteins / Q000235:genetics*; D004843:Epistasis, Genetic; D005260:Female; D005838:Genotype; D006801:Humans; D053762:Interleukin-12 Subunit p40 / Q000235:genetics*; D016015:Logistic Models; D008285:Major Histocompatibility Complex / Q000235:genetics*; D008297:Male; D020641:Polymorphism, Single Nucleotide; D011565:Psoriasis / Q000453:epidemiology / Q000235:genetics*; D012306:Risk; D055815:Young Adult
chemical_list: D055233:Cornified Envelope Proline-Rich Proteins; C500879:IL12B protein, human; D053762:Interleukin-12 Subunit p40; C524769:LCE3D protein, human