RGD Reference Report - Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus. - Rat Genome Database

Send us a Message



Submit Data |  Help |  Video Tutorials |  News |  Publications |  Download |  REST API |  Citing RGD |  Contact   

Phenotypic associations of genetic susceptibility loci in systemic lupus erythematosus.

Authors: Sanchez, E  Nadig, A  Richardson, BC  Freedman, BI  Kaufman, KM  Kelly, JA  Niewold, TB  Kamen, DL  Gilkeson, GS  Ziegler, JT  Langefeld, CD  Alarcon, GS  Edberg, JC  Ramsey-Goldman, R  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, ME  Sawalha, AH  Sawalha, Amr H 
Citation: Sanchez E, etal., Ann Rheum Dis. 2011 Jun 30.
RGD ID: 5147916
Pubmed: PMID:21719445   (View Abstract at PubMed)
PMCID: PMC3232181   (View Article at PubMed Central)
DOI: DOI:10.1136/ard.2011.154104   (Journal Full-text)

OBJECTIVE: 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 METHODS: 4001 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. RESULTS: Renal disorder was significantly correlated with the lupus risk allele in ITGAM (p=5.0x10(-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. CONCLUSION: Signifi 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.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
ITGAMHumanlupus nephritis  IAGP  RGD 
ItgamRatlupus nephritis  ISOITGAM (Homo sapiens) RGD 
ItgamMouselupus nephritis  ISOITGAM (Homo sapiens) RGD 
STAT4HumanOral Ulcer  IAGP associated with Lupus Erythematosus more ...RGD 
Stat4RatOral Ulcer  ISOSTAT4 (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
Stat4MouseOral Ulcer  ISOSTAT4 (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
FCGR2AHumansystemic lupus erythematosus  IAGP  RGD 
Fcgr2aRatsystemic lupus erythematosus  ISOFCGR2A (Homo sapiens) RGD 
Fcgr3Mousesystemic lupus erythematosus  ISOFCGR2A (Homo sapiens) RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
STAT4HumanOral ulcer  IAGP associated with Lupus Erythematosus more ...RGD 
Objects Annotated

Genes (Rattus norvegicus)
Fcgr2a  (Fc gamma receptor 2A)
Itgam  (integrin subunit alpha M)
Stat4  (signal transducer and activator of transcription 4)

Genes (Mus musculus)
Fcgr3  (Fc receptor, IgG, low affinity III)
Itgam  (integrin alpha M)
Stat4  (signal transducer and activator of transcription 4)

Genes (Homo sapiens)
FCGR2A  (Fc gamma receptor IIa)
ITGAM  (integrin subunit alpha M)
STAT4  (signal transducer and activator of transcription 4)


Additional Information