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Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis
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Zeitschriftentitel: | Arthritis & Rheumatism |
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Personen und Körperschaften: | , , , , , , , , |
In: | Arthritis & Rheumatism, 60, 2009, 7, S. 2124-2130 |
Format: | E-Article |
Sprache: | Englisch |
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author_facet |
Prahalad, Sampath Hansen, Sterling Whiting, April Guthery, Stephen L. Clifford, Bronte McNally, Bernadette Zeft, Andrew S. Bohnsack, John F. Jorde, Lynn B. Prahalad, Sampath Hansen, Sterling Whiting, April Guthery, Stephen L. Clifford, Bronte McNally, Bernadette Zeft, Andrew S. Bohnsack, John F. Jorde, Lynn B. |
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author |
Prahalad, Sampath Hansen, Sterling Whiting, April Guthery, Stephen L. Clifford, Bronte McNally, Bernadette Zeft, Andrew S. Bohnsack, John F. Jorde, Lynn B. |
spellingShingle |
Prahalad, Sampath Hansen, Sterling Whiting, April Guthery, Stephen L. Clifford, Bronte McNally, Bernadette Zeft, Andrew S. Bohnsack, John F. Jorde, Lynn B. Arthritis & Rheumatism Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis Pharmacology (medical) Immunology Rheumatology Immunology and Allergy |
author_sort |
prahalad, sampath |
spelling |
Prahalad, Sampath Hansen, Sterling Whiting, April Guthery, Stephen L. Clifford, Bronte McNally, Bernadette Zeft, Andrew S. Bohnsack, John F. Jorde, Lynn B. 0004-3591 1529-0131 Wiley Pharmacology (medical) Immunology Rheumatology Immunology and Allergy http://dx.doi.org/10.1002/art.24618 <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Subtypes of juvenile idiopathic arthritis (JIA) share phenotypic features with other autoimmune disorders. We investigated several genetic variants associated with rheumatoid arthritis (RA) and other autoimmune disorders for association with JIA to test the hypothesis that clinically distinct phenotypes share common genetic susceptibility factors.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Cases were 445 children with JIA, and controls were 643 healthy adults. Using the TaqMan assay, subjects were genotyped for 8 single‐nucleotide polymorphisms in 7 loci including rs10499194 and rs6920220 in the <jats:italic>TNFAIP3</jats:italic> locus, rs6679677 in the <jats:italic>RSBN1</jats:italic> locus, rs17696736 in the <jats:italic>C12orf30</jats:italic> locus, rs3761847 in the <jats:italic>TRAF1</jats:italic>/<jats:italic>C5</jats:italic> locus, rs2104286 in the <jats:italic>IL2RA</jats:italic> locus, rs7574865 in the <jats:italic>STAT4</jats:italic> locus, and rs2542151 in the <jats:italic>PTPN2</jats:italic> locus. Alleles and genotypes were analyzed for association with JIA and JIA subtypes. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The strongest associations with JIA risk or protection were observed for <jats:italic>TNFAIP3</jats:italic> variants rs10499194 (OR 0.74 [95% CI 0.61–0.91], <jats:italic>P</jats:italic> < 0.004) and rs6920220 (OR 1.30 [95% CI 1.05–1.61], <jats:italic>P</jats:italic> = 0.015). We also observed associations between JIA and both <jats:italic>STAT4</jats:italic> (OR 1.24 [95% CI 1.02–1.51], <jats:italic>P</jats:italic> = 0.029) and <jats:italic>C12orf30</jats:italic> (OR 1.20 [95% CI 1.01–1.43], <jats:italic>P</jats:italic> = 0.041) variants. The <jats:italic>PTPN2</jats:italic> variant rs2542151 deviated from Hardy‐Weinberg equilibrium and was excluded from analyses. Variants in <jats:italic>IL2RA</jats:italic>, <jats:italic>TRAF1/C5</jats:italic>, and <jats:italic>RSBN1</jats:italic> were not associated with JIA. After stratification by JIA subtype, the <jats:italic>TNFAIP3</jats:italic> and <jats:italic>C12orf30</jats:italic> variants were associated with oligoarticular JIA, while the <jats:italic>STAT4</jats:italic> variant was associated primarily with polyarticular JIA.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>We have demonstrated associations between JIA and variants in the <jats:italic>TNFAIP3</jats:italic>, <jats:italic>STAT4</jats:italic>, and <jats:italic>C12orf30</jats:italic> regions that have previously shown associations with other autoimmune diseases, including RA and systemic lupus erythematosus. Our results suggest that clinically distinct autoimmune phenotypes share common genetic susceptibility factors.</jats:p></jats:sec> Variants in <i>TNFAIP3</i>, <i>STAT4</i>, and <i>C12orf30</i> loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis Arthritis & Rheumatism |
doi_str_mv |
10.1002/art.24618 |
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prahalad2009variantsintnfaip3stat4andc12orf30lociassociatedwithmultipleautoimmunediseasesarealsoassociatedwithjuvenileidiopathicarthritis |
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2009 |
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Arthritis & Rheumatism |
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title |
Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_unstemmed |
Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_full |
Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_fullStr |
Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_full_unstemmed |
Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_short |
Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_sort |
variants in <i>tnfaip3</i>, <i>stat4</i>, and <i>c12orf30</i> loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
topic |
Pharmacology (medical) Immunology Rheumatology Immunology and Allergy |
url |
http://dx.doi.org/10.1002/art.24618 |
publishDate |
2009 |
physical |
2124-2130 |
description |
<jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Subtypes of juvenile idiopathic arthritis (JIA) share phenotypic features with other autoimmune disorders. We investigated several genetic variants associated with rheumatoid arthritis (RA) and other autoimmune disorders for association with JIA to test the hypothesis that clinically distinct phenotypes share common genetic susceptibility factors.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Cases were 445 children with JIA, and controls were 643 healthy adults. Using the TaqMan assay, subjects were genotyped for 8 single‐nucleotide polymorphisms in 7 loci including rs10499194 and rs6920220 in the <jats:italic>TNFAIP3</jats:italic> locus, rs6679677 in the <jats:italic>RSBN1</jats:italic> locus, rs17696736 in the <jats:italic>C12orf30</jats:italic> locus, rs3761847 in the <jats:italic>TRAF1</jats:italic>/<jats:italic>C5</jats:italic> locus, rs2104286 in the <jats:italic>IL2RA</jats:italic> locus, rs7574865 in the <jats:italic>STAT4</jats:italic> locus, and rs2542151 in the <jats:italic>PTPN2</jats:italic> locus. Alleles and genotypes were analyzed for association with JIA and JIA subtypes. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The strongest associations with JIA risk or protection were observed for <jats:italic>TNFAIP3</jats:italic> variants rs10499194 (OR 0.74 [95% CI 0.61–0.91], <jats:italic>P</jats:italic> < 0.004) and rs6920220 (OR 1.30 [95% CI 1.05–1.61], <jats:italic>P</jats:italic> = 0.015). We also observed associations between JIA and both <jats:italic>STAT4</jats:italic> (OR 1.24 [95% CI 1.02–1.51], <jats:italic>P</jats:italic> = 0.029) and <jats:italic>C12orf30</jats:italic> (OR 1.20 [95% CI 1.01–1.43], <jats:italic>P</jats:italic> = 0.041) variants. The <jats:italic>PTPN2</jats:italic> variant rs2542151 deviated from Hardy‐Weinberg equilibrium and was excluded from analyses. Variants in <jats:italic>IL2RA</jats:italic>, <jats:italic>TRAF1/C5</jats:italic>, and <jats:italic>RSBN1</jats:italic> were not associated with JIA. After stratification by JIA subtype, the <jats:italic>TNFAIP3</jats:italic> and <jats:italic>C12orf30</jats:italic> variants were associated with oligoarticular JIA, while the <jats:italic>STAT4</jats:italic> variant was associated primarily with polyarticular JIA.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>We have demonstrated associations between JIA and variants in the <jats:italic>TNFAIP3</jats:italic>, <jats:italic>STAT4</jats:italic>, and <jats:italic>C12orf30</jats:italic> regions that have previously shown associations with other autoimmune diseases, including RA and systemic lupus erythematosus. Our results suggest that clinically distinct autoimmune phenotypes share common genetic susceptibility factors.</jats:p></jats:sec> |
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author | Prahalad, Sampath, Hansen, Sterling, Whiting, April, Guthery, Stephen L., Clifford, Bronte, McNally, Bernadette, Zeft, Andrew S., Bohnsack, John F., Jorde, Lynn B. |
author_facet | Prahalad, Sampath, Hansen, Sterling, Whiting, April, Guthery, Stephen L., Clifford, Bronte, McNally, Bernadette, Zeft, Andrew S., Bohnsack, John F., Jorde, Lynn B., Prahalad, Sampath, Hansen, Sterling, Whiting, April, Guthery, Stephen L., Clifford, Bronte, McNally, Bernadette, Zeft, Andrew S., Bohnsack, John F., Jorde, Lynn B. |
author_sort | prahalad, sampath |
container_issue | 7 |
container_start_page | 2124 |
container_title | Arthritis & Rheumatism |
container_volume | 60 |
description | <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Subtypes of juvenile idiopathic arthritis (JIA) share phenotypic features with other autoimmune disorders. We investigated several genetic variants associated with rheumatoid arthritis (RA) and other autoimmune disorders for association with JIA to test the hypothesis that clinically distinct phenotypes share common genetic susceptibility factors.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Cases were 445 children with JIA, and controls were 643 healthy adults. Using the TaqMan assay, subjects were genotyped for 8 single‐nucleotide polymorphisms in 7 loci including rs10499194 and rs6920220 in the <jats:italic>TNFAIP3</jats:italic> locus, rs6679677 in the <jats:italic>RSBN1</jats:italic> locus, rs17696736 in the <jats:italic>C12orf30</jats:italic> locus, rs3761847 in the <jats:italic>TRAF1</jats:italic>/<jats:italic>C5</jats:italic> locus, rs2104286 in the <jats:italic>IL2RA</jats:italic> locus, rs7574865 in the <jats:italic>STAT4</jats:italic> locus, and rs2542151 in the <jats:italic>PTPN2</jats:italic> locus. Alleles and genotypes were analyzed for association with JIA and JIA subtypes. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The strongest associations with JIA risk or protection were observed for <jats:italic>TNFAIP3</jats:italic> variants rs10499194 (OR 0.74 [95% CI 0.61–0.91], <jats:italic>P</jats:italic> < 0.004) and rs6920220 (OR 1.30 [95% CI 1.05–1.61], <jats:italic>P</jats:italic> = 0.015). We also observed associations between JIA and both <jats:italic>STAT4</jats:italic> (OR 1.24 [95% CI 1.02–1.51], <jats:italic>P</jats:italic> = 0.029) and <jats:italic>C12orf30</jats:italic> (OR 1.20 [95% CI 1.01–1.43], <jats:italic>P</jats:italic> = 0.041) variants. The <jats:italic>PTPN2</jats:italic> variant rs2542151 deviated from Hardy‐Weinberg equilibrium and was excluded from analyses. Variants in <jats:italic>IL2RA</jats:italic>, <jats:italic>TRAF1/C5</jats:italic>, and <jats:italic>RSBN1</jats:italic> were not associated with JIA. After stratification by JIA subtype, the <jats:italic>TNFAIP3</jats:italic> and <jats:italic>C12orf30</jats:italic> variants were associated with oligoarticular JIA, while the <jats:italic>STAT4</jats:italic> variant was associated primarily with polyarticular JIA.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>We have demonstrated associations between JIA and variants in the <jats:italic>TNFAIP3</jats:italic>, <jats:italic>STAT4</jats:italic>, and <jats:italic>C12orf30</jats:italic> regions that have previously shown associations with other autoimmune diseases, including RA and systemic lupus erythematosus. Our results suggest that clinically distinct autoimmune phenotypes share common genetic susceptibility factors.</jats:p></jats:sec> |
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imprint | Wiley, 2009 |
imprint_str_mv | Wiley, 2009 |
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spelling | Prahalad, Sampath Hansen, Sterling Whiting, April Guthery, Stephen L. Clifford, Bronte McNally, Bernadette Zeft, Andrew S. Bohnsack, John F. Jorde, Lynn B. 0004-3591 1529-0131 Wiley Pharmacology (medical) Immunology Rheumatology Immunology and Allergy http://dx.doi.org/10.1002/art.24618 <jats:title>Abstract</jats:title><jats:sec><jats:title>Objective</jats:title><jats:p>Subtypes of juvenile idiopathic arthritis (JIA) share phenotypic features with other autoimmune disorders. We investigated several genetic variants associated with rheumatoid arthritis (RA) and other autoimmune disorders for association with JIA to test the hypothesis that clinically distinct phenotypes share common genetic susceptibility factors.</jats:p></jats:sec><jats:sec><jats:title>Methods</jats:title><jats:p>Cases were 445 children with JIA, and controls were 643 healthy adults. Using the TaqMan assay, subjects were genotyped for 8 single‐nucleotide polymorphisms in 7 loci including rs10499194 and rs6920220 in the <jats:italic>TNFAIP3</jats:italic> locus, rs6679677 in the <jats:italic>RSBN1</jats:italic> locus, rs17696736 in the <jats:italic>C12orf30</jats:italic> locus, rs3761847 in the <jats:italic>TRAF1</jats:italic>/<jats:italic>C5</jats:italic> locus, rs2104286 in the <jats:italic>IL2RA</jats:italic> locus, rs7574865 in the <jats:italic>STAT4</jats:italic> locus, and rs2542151 in the <jats:italic>PTPN2</jats:italic> locus. Alleles and genotypes were analyzed for association with JIA and JIA subtypes. Odds ratios (ORs) and 95% confidence intervals (95% CIs) were calculated.</jats:p></jats:sec><jats:sec><jats:title>Results</jats:title><jats:p>The strongest associations with JIA risk or protection were observed for <jats:italic>TNFAIP3</jats:italic> variants rs10499194 (OR 0.74 [95% CI 0.61–0.91], <jats:italic>P</jats:italic> < 0.004) and rs6920220 (OR 1.30 [95% CI 1.05–1.61], <jats:italic>P</jats:italic> = 0.015). We also observed associations between JIA and both <jats:italic>STAT4</jats:italic> (OR 1.24 [95% CI 1.02–1.51], <jats:italic>P</jats:italic> = 0.029) and <jats:italic>C12orf30</jats:italic> (OR 1.20 [95% CI 1.01–1.43], <jats:italic>P</jats:italic> = 0.041) variants. The <jats:italic>PTPN2</jats:italic> variant rs2542151 deviated from Hardy‐Weinberg equilibrium and was excluded from analyses. Variants in <jats:italic>IL2RA</jats:italic>, <jats:italic>TRAF1/C5</jats:italic>, and <jats:italic>RSBN1</jats:italic> were not associated with JIA. After stratification by JIA subtype, the <jats:italic>TNFAIP3</jats:italic> and <jats:italic>C12orf30</jats:italic> variants were associated with oligoarticular JIA, while the <jats:italic>STAT4</jats:italic> variant was associated primarily with polyarticular JIA.</jats:p></jats:sec><jats:sec><jats:title>Conclusion</jats:title><jats:p>We have demonstrated associations between JIA and variants in the <jats:italic>TNFAIP3</jats:italic>, <jats:italic>STAT4</jats:italic>, and <jats:italic>C12orf30</jats:italic> regions that have previously shown associations with other autoimmune diseases, including RA and systemic lupus erythematosus. Our results suggest that clinically distinct autoimmune phenotypes share common genetic susceptibility factors.</jats:p></jats:sec> Variants in <i>TNFAIP3</i>, <i>STAT4</i>, and <i>C12orf30</i> loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis Arthritis & Rheumatism |
spellingShingle | Prahalad, Sampath, Hansen, Sterling, Whiting, April, Guthery, Stephen L., Clifford, Bronte, McNally, Bernadette, Zeft, Andrew S., Bohnsack, John F., Jorde, Lynn B., Arthritis & Rheumatism, Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis, Pharmacology (medical), Immunology, Rheumatology, Immunology and Allergy |
title | Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_full | Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_fullStr | Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_full_unstemmed | Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_short | Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_sort | variants in <i>tnfaip3</i>, <i>stat4</i>, and <i>c12orf30</i> loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
title_unstemmed | Variants in TNFAIP3, STAT4, and C12orf30 loci associated with multiple autoimmune diseases are also associated with juvenile idiopathic arthritis |
topic | Pharmacology (medical), Immunology, Rheumatology, Immunology and Allergy |
url | http://dx.doi.org/10.1002/art.24618 |