TY - JOUR
T1 - Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome
AU - Levinson, Ralph D.
AU - Park, Min S.
AU - Rikkers, Sarah M.
AU - Reed, Elaine F.
AU - Smith, Justine R.
AU - Martin, Tammy M.
AU - Rosenbaum, James T.
AU - Foster, C. Stephen
AU - Sherman, Mark D.
AU - Holland, Gary N.
PY - 2003/2/1
Y1 - 2003/2/1
N2 - PURPOSE. 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 αβ dimer encoded by HLA-DQA1*01/DQB1*05 may be particularly important in conferring risk for development of this disease.
AB - PURPOSE. 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 αβ dimer encoded by HLA-DQA1*01/DQB1*05 may be particularly important in conferring risk for development of this disease.
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U2 - 10.1167/iovs.02-0376
DO - 10.1167/iovs.02-0376
M3 - Article
C2 - 12556395
AN - SCOPUS:0037311474
SN - 0146-0404
VL - 44
SP - 653
EP - 657
JO - Investigative Ophthalmology and Visual Science
JF - Investigative Ophthalmology and Visual Science
IS - 2
ER -