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Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus
- Sanchez, E (author)
- Nadig, A (author)
- Richardson, BC (author)
- show more...
- Freedman, BI (author)
- Kaufman, KM (author)
- Kelly, JA (author)
- Niewold, TB (author)
- Kamen, DL (author)
- Gilkeson, GS (author)
- Ziegler, JT (author)
- Langefeld, CD (author)
- Alarcon, GS (author)
- Edberg, JC (author)
- Ramsey-Goldman, R (author)
- Petri, M (author)
- Brown, EE (author)
- Kimberly, RP (author)
- Reveille, JD (author)
- Vila, LM (author)
- Merrill, JT (author)
- Anaya, JM (author)
- James, JA (author)
- Pons-Estel, BA (author)
- Martin, J (author)
- Park, SY (author)
- Bang, SY (author)
- Bae, SC (author)
- Moser, KL (author)
- Vyse, TJ (author)
- Criswell, LA (author)
- Gaffney, PM (author)
- Tsao, BP (author)
- Jacob, CO (author)
- Harley, JB (author)
- Alarcon-Riquelme, ME (author)
- Sawalha, AH (author)
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- 2011-06-30
- 2011
- English.
- In: Annals of the rheumatic diseases. - : BMJ. - 1468-2060 .- 0003-4967. ; 70:10, s. 1752-1757
- Journal article (peer-reviewed)
Abstract
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- Systemic lupus erythematosus is a clinically heterogeneous autoimmune disease. A number of genetic loci that increase lupus susceptibility have been established. This study examines if these genetic loci also contribute to the clinical heterogeneity in lupus.Materials and methods4001 European-derived, 1547 Hispanic, 1590 African-American and 1191 Asian lupus patients were genotyped for 16 confirmed lupus susceptibility loci. Ancestry informative markers were genotyped to calculate and adjust for admixture. The association between the risk allele in each locus was determined and compared in patients with and without the various clinical manifestations included in the ACR criteria.ResultsRenal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0×10−6, OR 1.25, 95% CI 1.12 to 1.35) and in TNFSF4 (p=0.0013, OR 1.14, 95% CI 1.07 to 1.25). Other significant findings include the association between risk alleles in FCGR2A and malar rash (p=0.0031, OR 1.11, 95% CI 1.17 to 1.33), ITGAM and discoid rash (p=0.0020, OR 1.20, 95% CI 1.06 to 1.33), STAT4 and protection from oral ulcers (p=0.0027, OR 0.89, 95% CI 0.83 to 0.96) and IL21 and haematological disorder (p=0.0027, OR 1.13, 95% CI 1.04 to 1.22). All these associations are significant with a false discovery rate of <0.05 and pass the significance threshold using Bonferroni correction for multiple testing.ConclusionSignifi cant associations were found between clinical manifestations and the FCGR2A, ITGAM, STAT4, TNSF4 and IL21 genes. The findings suggest that genetic profiling might be a useful tool to predict disease manifestations in lupus patients in the future.
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- Sanchez, E
- Nadig, A
- Richardson, BC
- Freedman, BI
- Kaufman, KM
- Kelly, JA
- show more...
- Niewold, TB
- Kamen, DL
- Gilkeson, GS
- Ziegler, JT
- Langefeld, CD
- Alarcon, GS
- Edberg, JC
- Ramsey-Goldman, ...
- Petri, M
- Brown, EE
- Kimberly, RP
- Reveille, JD
- Vila, LM
- Merrill, JT
- Anaya, JM
- James, JA
- Pons-Estel, BA
- Martin, J
- Park, SY
- Bang, SY
- Bae, SC
- Moser, KL
- Vyse, TJ
- Criswell, LA
- Gaffney, PM
- Tsao, BP
- Jacob, CO
- Harley, JB
- Alarcon-Riquelme ...
- Sawalha, AH
- show less...
- Articles in the publication
- Annals of the rh ...
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- Karolinska Institutet
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