Abstract
Rheumatoid arthritis (RA) is an inflammatory disease with a complex genetic component. An association between RA and the human leukocyte antigen (HLA) complex has long been observed in many different populations, and most studies have focused on a direct role for the HLA-DRB1 "shared epitope" in disease susceptibility. We have performed an extensive haplotype analysis, using 54 markers distributed across the entire HLA complex, in a set of 469 multicase families with RA. The results show that, in addition to associations with the DRB1 alleles, at least two additional genetic effects are present within the major histocompatibility complex. One of these lies within a 497-kb region in the central portion of the HLA complex, an interval that excludes DRB1. This genetic risk factor is present on a segment of a highly conserved ancestral A1-B8-DRB1*03 (8.1) haplotype. Additional risk genes may also be present in the HLA class I region in a subset of DRB1*0404 haplotypes. These data emphasize the importance of defining haplotypes when trying to understand the HLA associations with disease, and they clearly demonstrate that such associations with RA are complex and cannot be completely explained by the DRB1 locus.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 585-594 |
| Number of pages | 10 |
| Journal | American Journal of Human Genetics |
| Volume | 71 |
| Issue number | 3 |
| DOIs | |
| State | Published - Sep 2002 |
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ASJC Scopus subject areas
- Genetics
Cite this
Dissecting the genetic complexity of the association between human leukocyte antigens and rheumatoid arthritis. / Jawaheer, Damini; Li, Wentian; Graham, Robert R.; Chen, Wei; Damle, Aarti; Xiao, Xiangli; Monteiro, Joanita; Khalili, Houman; Lee, Annette; Lundsten, Robert; Begovich, Ann; Bugawan, Teodorica; Erlich, Henry; Elder, James T.; Criswell, Lindsey A.; Seldin, Michael F; Amos, Christopher I.; Behrens, Timothy W.; Gregersen, Peter K.
In: American Journal of Human Genetics, Vol. 71, No. 3, 09.2002, p. 585-594.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Dissecting the genetic complexity of the association between human leukocyte antigens and rheumatoid arthritis
AU - Jawaheer, Damini
AU - Li, Wentian
AU - Graham, Robert R.
AU - Chen, Wei
AU - Damle, Aarti
AU - Xiao, Xiangli
AU - Monteiro, Joanita
AU - Khalili, Houman
AU - Lee, Annette
AU - Lundsten, Robert
AU - Begovich, Ann
AU - Bugawan, Teodorica
AU - Erlich, Henry
AU - Elder, James T.
AU - Criswell, Lindsey A.
AU - Seldin, Michael F
AU - Amos, Christopher I.
AU - Behrens, Timothy W.
AU - Gregersen, Peter K.
PY - 2002/9
Y1 - 2002/9
N2 - Rheumatoid arthritis (RA) is an inflammatory disease with a complex genetic component. An association between RA and the human leukocyte antigen (HLA) complex has long been observed in many different populations, and most studies have focused on a direct role for the HLA-DRB1 "shared epitope" in disease susceptibility. We have performed an extensive haplotype analysis, using 54 markers distributed across the entire HLA complex, in a set of 469 multicase families with RA. The results show that, in addition to associations with the DRB1 alleles, at least two additional genetic effects are present within the major histocompatibility complex. One of these lies within a 497-kb region in the central portion of the HLA complex, an interval that excludes DRB1. This genetic risk factor is present on a segment of a highly conserved ancestral A1-B8-DRB1*03 (8.1) haplotype. Additional risk genes may also be present in the HLA class I region in a subset of DRB1*0404 haplotypes. These data emphasize the importance of defining haplotypes when trying to understand the HLA associations with disease, and they clearly demonstrate that such associations with RA are complex and cannot be completely explained by the DRB1 locus.
AB - Rheumatoid arthritis (RA) is an inflammatory disease with a complex genetic component. An association between RA and the human leukocyte antigen (HLA) complex has long been observed in many different populations, and most studies have focused on a direct role for the HLA-DRB1 "shared epitope" in disease susceptibility. We have performed an extensive haplotype analysis, using 54 markers distributed across the entire HLA complex, in a set of 469 multicase families with RA. The results show that, in addition to associations with the DRB1 alleles, at least two additional genetic effects are present within the major histocompatibility complex. One of these lies within a 497-kb region in the central portion of the HLA complex, an interval that excludes DRB1. This genetic risk factor is present on a segment of a highly conserved ancestral A1-B8-DRB1*03 (8.1) haplotype. Additional risk genes may also be present in the HLA class I region in a subset of DRB1*0404 haplotypes. These data emphasize the importance of defining haplotypes when trying to understand the HLA associations with disease, and they clearly demonstrate that such associations with RA are complex and cannot be completely explained by the DRB1 locus.
UR - http://www.scopus.com/inward/record.url?scp=18544362452&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=18544362452&partnerID=8YFLogxK
U2 - 10.1086/342407
DO - 10.1086/342407
M3 - Article
C2 - 12181776
AN - SCOPUS:18544362452
VL - 71
SP - 585
EP - 594
JO - American Journal of Human Genetics
JF - American Journal of Human Genetics
SN - 0002-9297
IS - 3
ER -