Abstract
Objective. The SLC11A1 (formerly called NRAMP1) gene is important in natural resistance to a variety of intracellular infections mediated by macrophages and has been proposed as a candidate gene for autoimmune disease susceptibility. The aim of this study was to examine susceptibility in Finnish patients with persistent oligoarticular and polyarticular rheumatoid factor (RF)-negative juvenile idiopathic arthritis (JIA) due to the presence of the SLC11A1 locus on chromosome 2. Methods. A total of 234 Finnish JIA nuclear families and 639 elderly Finnish controls without a history of JIA were evaluated for association with JIA at 3 intragenic single-nucleotide polymorphisms: an intragenie insertion/deletion, a promoter microsatellite (NRAMP1), and a 3′ microsatellite (D2S1471). Results. Analysis of marker haplotypes demonstrated a strong association of Finnish JIA with 6-marker, 4-marker, and 2-marker haplotypes. Most impressively, 1 of the 6-marker haplotypes showed an odds ratio (OR) of 4.0 (95% confidence interval [95% CI] 2.6-6.2) in all JIA patients, 3.5 (95% CI 1.9-6.5) in those with persistent oligoarticular JIA, and 4.1 (95% CI 2.5-6.7) in those with polyarticular RF-negative JIA. Stratification of the haplotype data suggested that susceptibility to JIA in the haplotype spanning the SLC11A1 locus is independent (P < 0.01) of an association with a DRB1 JIA shared epitope (DRB1*JIASE) that includes well-characterized strong susceptibility to DRB1*08 and *11 alleles. This SLC11A1 haplotype also had an additive effect with DRB1*JIASE in those with polyarticular, but not those with persistent oligoarticular, disease (P = 0.06, OR 2.9 [95% CI 0.9-9.2] versus P = 0.5, OR 1.6 [95% CI 0.4-6.0]). Conclusion. Taken together, these data provide support for the existence of a locus at or near SLC11A1 that is a strong susceptibility factor for JIA in Finnish patients.
| Original language | English (US) |
|---|---|
| Pages (from-to) | 247-256 |
| Number of pages | 10 |
| Journal | Arthritis and Rheumatism |
| Volume | 52 |
| Issue number | 1 |
| DOIs | |
| State | Published - Jan 2005 |
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ASJC Scopus subject areas
- Immunology
- Rheumatology
Cite this
Association of SLC11A1 (NRAMP1) with persistent oligoarticular and polyarticular rheumatoid factor-negative juvenile idiopathic arthritis in Finnish patients : Haplotype analysis in Finnish families. / Runstadler, Jonathan A.; Säilä, Hanna; Savolainen, Anneli; Leirisalo-Repo, Marjatta; Aho, Kimmo; Tuomilehto-Wolf, Eva; Tuomilehto, Jaakko; Seldin, Michael F.
In: Arthritis and Rheumatism, Vol. 52, No. 1, 01.2005, p. 247-256.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Association of SLC11A1 (NRAMP1) with persistent oligoarticular and polyarticular rheumatoid factor-negative juvenile idiopathic arthritis in Finnish patients
T2 - Haplotype analysis in Finnish families
AU - Runstadler, Jonathan A.
AU - Säilä, Hanna
AU - Savolainen, Anneli
AU - Leirisalo-Repo, Marjatta
AU - Aho, Kimmo
AU - Tuomilehto-Wolf, Eva
AU - Tuomilehto, Jaakko
AU - Seldin, Michael F
PY - 2005/1
Y1 - 2005/1
N2 - Objective. The SLC11A1 (formerly called NRAMP1) gene is important in natural resistance to a variety of intracellular infections mediated by macrophages and has been proposed as a candidate gene for autoimmune disease susceptibility. The aim of this study was to examine susceptibility in Finnish patients with persistent oligoarticular and polyarticular rheumatoid factor (RF)-negative juvenile idiopathic arthritis (JIA) due to the presence of the SLC11A1 locus on chromosome 2. Methods. A total of 234 Finnish JIA nuclear families and 639 elderly Finnish controls without a history of JIA were evaluated for association with JIA at 3 intragenic single-nucleotide polymorphisms: an intragenie insertion/deletion, a promoter microsatellite (NRAMP1), and a 3′ microsatellite (D2S1471). Results. Analysis of marker haplotypes demonstrated a strong association of Finnish JIA with 6-marker, 4-marker, and 2-marker haplotypes. Most impressively, 1 of the 6-marker haplotypes showed an odds ratio (OR) of 4.0 (95% confidence interval [95% CI] 2.6-6.2) in all JIA patients, 3.5 (95% CI 1.9-6.5) in those with persistent oligoarticular JIA, and 4.1 (95% CI 2.5-6.7) in those with polyarticular RF-negative JIA. Stratification of the haplotype data suggested that susceptibility to JIA in the haplotype spanning the SLC11A1 locus is independent (P < 0.01) of an association with a DRB1 JIA shared epitope (DRB1*JIASE) that includes well-characterized strong susceptibility to DRB1*08 and *11 alleles. This SLC11A1 haplotype also had an additive effect with DRB1*JIASE in those with polyarticular, but not those with persistent oligoarticular, disease (P = 0.06, OR 2.9 [95% CI 0.9-9.2] versus P = 0.5, OR 1.6 [95% CI 0.4-6.0]). Conclusion. Taken together, these data provide support for the existence of a locus at or near SLC11A1 that is a strong susceptibility factor for JIA in Finnish patients.
AB - Objective. The SLC11A1 (formerly called NRAMP1) gene is important in natural resistance to a variety of intracellular infections mediated by macrophages and has been proposed as a candidate gene for autoimmune disease susceptibility. The aim of this study was to examine susceptibility in Finnish patients with persistent oligoarticular and polyarticular rheumatoid factor (RF)-negative juvenile idiopathic arthritis (JIA) due to the presence of the SLC11A1 locus on chromosome 2. Methods. A total of 234 Finnish JIA nuclear families and 639 elderly Finnish controls without a history of JIA were evaluated for association with JIA at 3 intragenic single-nucleotide polymorphisms: an intragenie insertion/deletion, a promoter microsatellite (NRAMP1), and a 3′ microsatellite (D2S1471). Results. Analysis of marker haplotypes demonstrated a strong association of Finnish JIA with 6-marker, 4-marker, and 2-marker haplotypes. Most impressively, 1 of the 6-marker haplotypes showed an odds ratio (OR) of 4.0 (95% confidence interval [95% CI] 2.6-6.2) in all JIA patients, 3.5 (95% CI 1.9-6.5) in those with persistent oligoarticular JIA, and 4.1 (95% CI 2.5-6.7) in those with polyarticular RF-negative JIA. Stratification of the haplotype data suggested that susceptibility to JIA in the haplotype spanning the SLC11A1 locus is independent (P < 0.01) of an association with a DRB1 JIA shared epitope (DRB1*JIASE) that includes well-characterized strong susceptibility to DRB1*08 and *11 alleles. This SLC11A1 haplotype also had an additive effect with DRB1*JIASE in those with polyarticular, but not those with persistent oligoarticular, disease (P = 0.06, OR 2.9 [95% CI 0.9-9.2] versus P = 0.5, OR 1.6 [95% CI 0.4-6.0]). Conclusion. Taken together, these data provide support for the existence of a locus at or near SLC11A1 that is a strong susceptibility factor for JIA in Finnish patients.
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UR - http://www.scopus.com/inward/citedby.url?scp=12344266551&partnerID=8YFLogxK
U2 - 10.1002/art.20772
DO - 10.1002/art.20772
M3 - Article
C2 - 15641099
AN - SCOPUS:12344266551
VL - 52
SP - 247
EP - 256
JO - Arthritis and Rheumatology
JF - Arthritis and Rheumatology
SN - 2326-5191
IS - 1
ER -