Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome

Ralph D. Levinson, Min S. Park, Sarah M. Rikkers, Elaine F. Reed, Justine R. Smith, Tammy Martin, James (Jim) Rosenbaum, C. Stephen Foster, Mark D. Sherman, Gary N. Holland

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Abstract

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.

Original languageEnglish (US)
Pages (from-to)653-657
Number of pages5
JournalInvestigative Ophthalmology and Visual Science
Volume44
Issue number2
DOIs
StatePublished - Feb 1 2003

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HLA Antigens
Alleles
Tubulointerstitial nephritis and uveitis
MHC Class I Genes
MHC Class II Genes
Linkage Disequilibrium
Genetic Markers
Haplotypes

ASJC Scopus subject areas

  • Ophthalmology

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Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome. / Levinson, Ralph D.; Park, Min S.; Rikkers, Sarah M.; Reed, Elaine F.; Smith, Justine R.; Martin, Tammy; Rosenbaum, James (Jim); Foster, C. Stephen; Sherman, Mark D.; Holland, Gary N.

In: Investigative Ophthalmology and Visual Science, Vol. 44, No. 2, 01.02.2003, p. 653-657.

Research output: Contribution to journalArticle

Levinson, Ralph D. ; Park, Min S. ; Rikkers, Sarah M. ; Reed, Elaine F. ; Smith, Justine R. ; Martin, Tammy ; Rosenbaum, James (Jim) ; Foster, C. Stephen ; Sherman, Mark D. ; Holland, Gary N. / Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome. In: Investigative Ophthalmology and Visual Science. 2003 ; Vol. 44, No. 2. pp. 653-657.
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title = "Strong associations between specific HLA-DQ and HLA-DR alleles and the tubulointerstitial nephritis and uveitis syndrome",
abstract = "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.",
author = "Levinson, {Ralph D.} and Park, {Min S.} and Rikkers, {Sarah M.} and Reed, {Elaine F.} and Smith, {Justine R.} and Tammy Martin and Rosenbaum, {James (Jim)} and Foster, {C. Stephen} and Sherman, {Mark D.} and Holland, {Gary N.}",
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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

AU - Rosenbaum, James (Jim)

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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