title: Haplotype-based analysis of ulcerative colitis risk loci identifies both IL2 and IL21 as susceptibility genes in Han Chinese.
abstract: BACKGROUND
  The incidence of ulcerative colitis (UC) varies between Western and Eastern ethnicities. A distinct genetic background may play a role in the differences. Until now, very little was known of the UC genetics in Asian populations. Here we performed a haplotype-based analysis of six known UC susceptibility loci in Han Chinese patients.
  
  
  METHODS
  In all, 245 UC patients and 300 healthy controls of Han Chinese descent were genotyped for 27 single nucleotide polymorphisms (SNPs), which cover the major haplotypes of the chromosome regions containing IL10, IL2/IL21, MYO9B, ECM1, MST1, and IL23R in Han Chinese.
  
  
  RESULTS
  In contrast to the tight linkage disequilibrium (LD) block of the IL2/IL21 region in Caucasians, IL2 and IL21 reside in two independent LD blocks in Han Chinese. The IL2 SNP rs2069762 (P = 7.0 × 10(-4) , odds ratio [OR] = 1.54, 95% confidence interval [CI] 1.20-1.99) and the IL21 SNP rs2055979 (P = 1.2 × 10(-4) , OR = 1.50, 95% CI 1.17-1.92) were independently associated with UC. We identified one risk haplotype in IL2 and another independent risk haplotype in IL21. In addition to the IL2/IL21 locus, we observed association of the TT genotype of SNP rs1545620 in MYO9B with UC (P = 0.0169; OR = 0.29, 95% CI 0.11-0.78) and association of rs17375018 in IL23R with pancolitis in Chinese UC patients (P = 0.002; OR = 2.38, 95% CI 1.41-4.02).
  
  
  CONCLUSIONS
  Our study confirmed the association of the IL2/IL21 region with UC in Han Chinese patients, and further implied both IL2 and IL21 as genetic risk factors for UC. Han Chinese UC patients share part of their genetic susceptibility with Caucasian patients.
authors.affiliation: Department of Gastroenterology, Peking Union Medical College Hospital, Chinese Academy of Medical Science and Peking Union Medical College, Beijing, P.R. China.
authors.forename: Jihua
authors.initials: J
authors.lastname: Shi
authors.forename: Lu
authors.initials: L
authors.lastname: Zhou
authors.forename: Alexandra
authors.initials: A
authors.lastname: Zhernakova
authors.forename: Jiaming
authors.initials: J
authors.lastname: Qian
authors.forename: Feng
authors.initials: F
authors.lastname: Zhu
authors.forename: Gang
authors.initials: G
authors.lastname: Sun
authors.forename: Liming
authors.initials: L
authors.lastname: Zhu
authors.forename: Xuejun
authors.initials: X
authors.lastname: Ma
authors.forename: Gerard
authors.initials: G
authors.lastname: Dijkstra
authors.forename: Cisca
authors.initials: C
authors.lastname: Wijmenga
authors.forename: Klaas Nico
authors.initials: KN
authors.lastname: Faber
authors.forename: Xinghua
authors.initials: X
authors.lastname: Lu
authors.forename: Rinse K
authors.initials: RK
authors.lastname: Weersma
mesh_terms: D000328:Adult; D044466:Asian People / Q000235:genetics; D016022:Case-Control Studies; D003093:Colitis, Ulcerative / Q000235:genetics*; D005260:Female; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006239:Haplotypes / Q000235:genetics*; D006801:Humans; D007376:Interleukin-2 / Q000235:genetics*; D007378:Interleukins / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D012307:Risk Factors; D000098546:Interleukin-21
chemical_list: D007376:Interleukin-2; D007378:Interleukins; D000098546:Interleukin-21