A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease

Tammy Martin, Ge Zhang, Jingchun Luo, Li Jin, Trudy M. Doyle, Barbara M. Rajska, Jessica E. Coffman, Justine R. Smith, Matthias D. Becker, Friederike Mackensen, Muhammad A. Khan, Ralph D. Levinson, H. Ralph Schumacher, N. Kevin Wade, James (Jim) Rosenbaum, John D. Reveille

Research output: Contribution to journalArticle

50 Citations (Scopus)

Abstract

Objective. Uveitis or intraocular inflammation is a major cause of visual loss. Acute anterior uveitis (AAU) affects ∼40% of patients with ankylosing spondylitis (AS) but also affects patients with no evidence of spondylarthritis. We sought to determine whether a unique genetic region could be implicated in a specific manifestation - AAU - of a multisystem, inflammatory, genetically complex disease, AS. Methods. Individuals from families multiplex for AAU were genotyped at 400 markers representing the ABI PRISM linkage map MD-10, and at the HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles. Among the family members with AAU, 76 affected sibpairs were analyzed (6 without concomitant AS, 12 discordant for AS, and 58 concordant for AS). Two-point and multipoint nonparametric linkage analyses were performed, and 1-parameter allele-sharing model logarithm of odds (LOD) scores were determined. Results. As previously reported for AS, linkage at the major histocompatibility complex region (chromosome 6p21) was evident, exhibiting the highest multipoint LOD score (4.96 at marker HLA-B). Strong linkage was seen at a region on chromosome 9p21-9p24, with a LOD score of 3.72 at marker D9S157. When compared with a companion cohort of AS families, the linkage at this region was found in association with AAU but not with AS. A third region on chromosome 1q23-1q31 was observed to have suggestive linkage (LOD 2.05 at marker D1S238), which overlaps with a region associated with AS. Conclusion. This is the first study in which a genetic region for AAU has been identified by genome-wide scan. Even though AS was highly prevalent in this cohort of families, a locus at chromosome 9p21-9p24 was identified that uniquely associates with AAU. Identifying the genetic perturbation at this region may advance our understanding of the mechanisms involved in tissue-specific pathology of complex inflammatory diseases.

Original languageEnglish (US)
Pages (from-to)269-274
Number of pages6
JournalArthritis and Rheumatism
Volume52
Issue number1
DOIs
StatePublished - Jan 2005

Fingerprint

Anterior Uveitis
Ankylosing Spondylitis
Acute Disease
Chromosomes
HLA-B Antigens
Spondylarthritis
Alleles
HLA-DRB1 Chains
Uveitis
Major Histocompatibility Complex
Genome
Pathology
Inflammation

ASJC Scopus subject areas

  • Immunology
  • Rheumatology

Cite this

A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease. / Martin, Tammy; Zhang, Ge; Luo, Jingchun; Jin, Li; Doyle, Trudy M.; Rajska, Barbara M.; Coffman, Jessica E.; Smith, Justine R.; Becker, Matthias D.; Mackensen, Friederike; Khan, Muhammad A.; Levinson, Ralph D.; Schumacher, H. Ralph; Wade, N. Kevin; Rosenbaum, James (Jim); Reveille, John D.

In: Arthritis and Rheumatism, Vol. 52, No. 1, 01.2005, p. 269-274.

Research output: Contribution to journalArticle

Martin, T, Zhang, G, Luo, J, Jin, L, Doyle, TM, Rajska, BM, Coffman, JE, Smith, JR, Becker, MD, Mackensen, F, Khan, MA, Levinson, RD, Schumacher, HR, Wade, NK, Rosenbaum, JJ & Reveille, JD 2005, 'A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease', Arthritis and Rheumatism, vol. 52, no. 1, pp. 269-274. https://doi.org/10.1002/art.20777
Martin, Tammy ; Zhang, Ge ; Luo, Jingchun ; Jin, Li ; Doyle, Trudy M. ; Rajska, Barbara M. ; Coffman, Jessica E. ; Smith, Justine R. ; Becker, Matthias D. ; Mackensen, Friederike ; Khan, Muhammad A. ; Levinson, Ralph D. ; Schumacher, H. Ralph ; Wade, N. Kevin ; Rosenbaum, James (Jim) ; Reveille, John D. / A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease. In: Arthritis and Rheumatism. 2005 ; Vol. 52, No. 1. pp. 269-274.
@article{2f47685ec2df40fbbcc528f732fb7a7d,
title = "A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease",
abstract = "Objective. Uveitis or intraocular inflammation is a major cause of visual loss. Acute anterior uveitis (AAU) affects ∼40{\%} of patients with ankylosing spondylitis (AS) but also affects patients with no evidence of spondylarthritis. We sought to determine whether a unique genetic region could be implicated in a specific manifestation - AAU - of a multisystem, inflammatory, genetically complex disease, AS. Methods. Individuals from families multiplex for AAU were genotyped at 400 markers representing the ABI PRISM linkage map MD-10, and at the HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles. Among the family members with AAU, 76 affected sibpairs were analyzed (6 without concomitant AS, 12 discordant for AS, and 58 concordant for AS). Two-point and multipoint nonparametric linkage analyses were performed, and 1-parameter allele-sharing model logarithm of odds (LOD) scores were determined. Results. As previously reported for AS, linkage at the major histocompatibility complex region (chromosome 6p21) was evident, exhibiting the highest multipoint LOD score (4.96 at marker HLA-B). Strong linkage was seen at a region on chromosome 9p21-9p24, with a LOD score of 3.72 at marker D9S157. When compared with a companion cohort of AS families, the linkage at this region was found in association with AAU but not with AS. A third region on chromosome 1q23-1q31 was observed to have suggestive linkage (LOD 2.05 at marker D1S238), which overlaps with a region associated with AS. Conclusion. This is the first study in which a genetic region for AAU has been identified by genome-wide scan. Even though AS was highly prevalent in this cohort of families, a locus at chromosome 9p21-9p24 was identified that uniquely associates with AAU. Identifying the genetic perturbation at this region may advance our understanding of the mechanisms involved in tissue-specific pathology of complex inflammatory diseases.",
author = "Tammy Martin and Ge Zhang and Jingchun Luo and Li Jin and Doyle, {Trudy M.} and Rajska, {Barbara M.} and Coffman, {Jessica E.} and Smith, {Justine R.} and Becker, {Matthias D.} and Friederike Mackensen and Khan, {Muhammad A.} and Levinson, {Ralph D.} and Schumacher, {H. Ralph} and Wade, {N. Kevin} and Rosenbaum, {James (Jim)} and Reveille, {John D.}",
year = "2005",
month = "1",
doi = "10.1002/art.20777",
language = "English (US)",
volume = "52",
pages = "269--274",
journal = "Arthritis and Rheumatology",
issn = "2326-5191",
publisher = "John Wiley and Sons Ltd",
number = "1",

}

TY - JOUR

T1 - A locus on chromosome 9p predisposes to a specific disease manifestation, acute anterior uveitis, in ankylosing spondylitis, a genetically complex, multisystem, inflammatory disease

AU - Martin, Tammy

AU - Zhang, Ge

AU - Luo, Jingchun

AU - Jin, Li

AU - Doyle, Trudy M.

AU - Rajska, Barbara M.

AU - Coffman, Jessica E.

AU - Smith, Justine R.

AU - Becker, Matthias D.

AU - Mackensen, Friederike

AU - Khan, Muhammad A.

AU - Levinson, Ralph D.

AU - Schumacher, H. Ralph

AU - Wade, N. Kevin

AU - Rosenbaum, James (Jim)

AU - Reveille, John D.

PY - 2005/1

Y1 - 2005/1

N2 - Objective. Uveitis or intraocular inflammation is a major cause of visual loss. Acute anterior uveitis (AAU) affects ∼40% of patients with ankylosing spondylitis (AS) but also affects patients with no evidence of spondylarthritis. We sought to determine whether a unique genetic region could be implicated in a specific manifestation - AAU - of a multisystem, inflammatory, genetically complex disease, AS. Methods. Individuals from families multiplex for AAU were genotyped at 400 markers representing the ABI PRISM linkage map MD-10, and at the HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles. Among the family members with AAU, 76 affected sibpairs were analyzed (6 without concomitant AS, 12 discordant for AS, and 58 concordant for AS). Two-point and multipoint nonparametric linkage analyses were performed, and 1-parameter allele-sharing model logarithm of odds (LOD) scores were determined. Results. As previously reported for AS, linkage at the major histocompatibility complex region (chromosome 6p21) was evident, exhibiting the highest multipoint LOD score (4.96 at marker HLA-B). Strong linkage was seen at a region on chromosome 9p21-9p24, with a LOD score of 3.72 at marker D9S157. When compared with a companion cohort of AS families, the linkage at this region was found in association with AAU but not with AS. A third region on chromosome 1q23-1q31 was observed to have suggestive linkage (LOD 2.05 at marker D1S238), which overlaps with a region associated with AS. Conclusion. This is the first study in which a genetic region for AAU has been identified by genome-wide scan. Even though AS was highly prevalent in this cohort of families, a locus at chromosome 9p21-9p24 was identified that uniquely associates with AAU. Identifying the genetic perturbation at this region may advance our understanding of the mechanisms involved in tissue-specific pathology of complex inflammatory diseases.

AB - Objective. Uveitis or intraocular inflammation is a major cause of visual loss. Acute anterior uveitis (AAU) affects ∼40% of patients with ankylosing spondylitis (AS) but also affects patients with no evidence of spondylarthritis. We sought to determine whether a unique genetic region could be implicated in a specific manifestation - AAU - of a multisystem, inflammatory, genetically complex disease, AS. Methods. Individuals from families multiplex for AAU were genotyped at 400 markers representing the ABI PRISM linkage map MD-10, and at the HLA-B, DRB1, DQA1, DQB1, and DPB1 alleles. Among the family members with AAU, 76 affected sibpairs were analyzed (6 without concomitant AS, 12 discordant for AS, and 58 concordant for AS). Two-point and multipoint nonparametric linkage analyses were performed, and 1-parameter allele-sharing model logarithm of odds (LOD) scores were determined. Results. As previously reported for AS, linkage at the major histocompatibility complex region (chromosome 6p21) was evident, exhibiting the highest multipoint LOD score (4.96 at marker HLA-B). Strong linkage was seen at a region on chromosome 9p21-9p24, with a LOD score of 3.72 at marker D9S157. When compared with a companion cohort of AS families, the linkage at this region was found in association with AAU but not with AS. A third region on chromosome 1q23-1q31 was observed to have suggestive linkage (LOD 2.05 at marker D1S238), which overlaps with a region associated with AS. Conclusion. This is the first study in which a genetic region for AAU has been identified by genome-wide scan. Even though AS was highly prevalent in this cohort of families, a locus at chromosome 9p21-9p24 was identified that uniquely associates with AAU. Identifying the genetic perturbation at this region may advance our understanding of the mechanisms involved in tissue-specific pathology of complex inflammatory diseases.

UR - http://www.scopus.com/inward/record.url?scp=19944433234&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=19944433234&partnerID=8YFLogxK

U2 - 10.1002/art.20777

DO - 10.1002/art.20777

M3 - Article

C2 - 15641041

AN - SCOPUS:19944433234

VL - 52

SP - 269

EP - 274

JO - Arthritis and Rheumatology

JF - Arthritis and Rheumatology

SN - 2326-5191

IS - 1

ER -