title: Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome.
abstract: OBJECTIVE
  To identify genetic markers for the tubulointerstitial nephritis and uveitis (TINU) syndrome by using human leukocyte antigen (HLA) genotyping.
  
  
  METHODS
  Eighteen patients who had TINU syndrome were evaluated at three institutions. Typing of class I and II genes was performed by using DNA-based techniques.
  
  
  RESULTS
  Significant associations were found with HLA-B14 (6/18 patients, 33.3%; control subjects, 5.5%; P = 0.0003; relative risk [RR] = 8.5), HLA-DQA1*01 (17/18 patients, 94.4%; control subjects, 46.6%, P = 0.0001; RR = 19.5), HLA-DQA1*0101 (14/18 patients, 77.8%; control subjects 22.2%; P < 0.0001; RR = 12.2), HLA-DQB1*05 (14/18 patients, 77.8%; control subjects 17.7%; P < 0.0001; RR = 16.3), HLA-DQB1*0501 (13/18 patients, 72.2%; control subjects 12.9%; P < 0.0001; RR = 17.6), HLA-DRB1*01 (14/18 patients, 77.8%; control subjects, 12.1%; P < 0.0001; RR = 25.5), and HLA-DRB1*0102 (13/18 patients, 72.2%; control subjects, 1.6%; P < 0.0001, RR = 167.1). The HLA haplotype most frequently identified in the study patients was HLA-DQA1*01/DQB1*05/DRB1*01 (13/18 patients, 72.2%).
  
  
  CONCLUSIONS
  TINU syndrome is strongly associated with HLA-DQA1*01, HLA-DQB1*05, and HLA-DRB1*01. The association with HLA-DRB1*0102 is one of the highest reported for any disease. Because these genes are in linkage disequilibrium, the role of the individual alleles is difficult to assess. Based on the results of the present study and on previously reported HLA associations in patients with TINU syndrome, the alphabeta dimer encoded by HLA-DQA1*01/DQB1*05 may be particularly important in conferring risk for development of this disease.
authors.affiliation: Ocular Inflammatory Disease Center, Jules Stein Eye Institute, UCLA Immunogenetics Center, University of California Los Angeles School of Medicine, Los Angeles, California 90095, USA. levinson@jsei.ucla.edu
authors.forename: Ralph D
authors.initials: RD
authors.lastname: Levinson
authors.forename: Min S
authors.initials: MS
authors.lastname: Park
authors.forename: Sarah M
authors.initials: SM
authors.lastname: Rikkers
authors.forename: Elaine F
authors.initials: EF
authors.lastname: Reed
authors.forename: Justine R
authors.initials: JR
authors.lastname: Smith
authors.forename: Tammy M
authors.initials: TM
authors.lastname: Martin
authors.forename: James T
authors.initials: JT
authors.lastname: Rosenbaum
authors.forename: C Stephen
authors.initials: CS
authors.lastname: Foster
authors.forename: Mark D
authors.initials: MD
authors.lastname: Sherman
authors.forename: Gary N
authors.initials: GN
authors.lastname: Holland
mesh_terms: D000293:Adolescent; D000328:Adult; D002648:Child; D004247:DNA / Q000032:analysis; D005260:Female; D005787:Gene Frequency; D008040:Genetic Linkage; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006801:Humans; D008297:Male; D008875:Middle Aged; D009395:Nephritis, Interstitial / Q000235:genetics*; D013577:Syndrome; D014605:Uveitis / Q000235:genetics*
chemical_list: D006683:HLA-DQ Antigens; D059848:HLA-DQ alpha-Chains; D059866:HLA-DQ beta-Chains; C069050:HLA-DQA1 antigen; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; D004247:DNA