RGD Reference Report - Association between SLE nephritis and polymorphic variants of the CRP and FcgammaRIIIa genes. - Rat Genome Database

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Association between SLE nephritis and polymorphic variants of the CRP and FcgammaRIIIa genes.

Authors: Jonsen, A  Gunnarsson, I  Gullstrand, B  Svenungsson, E  Bengtsson, AA  Nived, O  Lundberg, IE  Truedsson, L  Sturfelt, G 
Citation: Jonsen A, etal., Rheumatology (Oxford). 2007 Sep;46(9):1417-21. Epub 2007 Jun 27.
RGD ID: 5508454
Pubmed: PMID:17596285   (View Abstract at PubMed)
DOI: DOI:10.1093/rheumatology/kem167   (Journal Full-text)

OBJECTIVES: To study the relationship between clinical manifestations in systemic lupus erythematosus (SLE) with polymorphisms in suggested susceptibility genes encoding FcgammaRIIa, FcgammaRIIIa, FcgammaRIIIb, CRP and IL-1Ra. METHODS: Genetic polymorphisms were analysed in 323 unrelated SLE patients and 200 healthy blood donors. The genotype frequencies were compared between clinical subsets of SLE patients, as well as with healthy controls. Clinical manifestations included the ACR classification criteria. Nephritis was further classified according to WHO class on renal biopsy. RESULTS: Presence of a CRP4 A-allele was associated with SLE nephritis (P < 0.01) and inversely correlated with arthritis (P < 0.01), when comparing within the SLE group. The FcgammaRIIIa F/F genotype was also associated with nephritis (WHO class III and IV, P = 0.04 for the SLE group) and in combination with the CRP4 A-allele a stronger association was noted (P < 0.001). Furthermore, the FcgammaRIIIb NA2/NA2 genotype was associated with butterfly rash (P < 0.01). An association was found between seizures and the presence of both the FcgammaRIIa R/R and the FcgammaRIIIa F/F genotypes (P < 0.01) and an inverse correlation between serositis and the CRP4 A-allele when present together with the IL-1Ra 2-allele (P = 0.01). Furthermore, a combination of the FcgammaRIIa R/R genotype and CRP4 A-allele was associated with lymphopenia (P = 0.02) and a similar result was found for the combination of FcgammaRIIIa F/F and FcgammaRIIIb NA2/NA2 (P = 0.04). CONCLUSIONS: Polymorphic variants of the CRP and Fcgamma-receptor genes are associated with the clinical phenotype in SLE. Our findings suggest an immune complex-mediated pathogenesis in nephritis and seizures, while development of arthritis may depend on other pathogenetic pathways.



RGD Manual Disease Annotations    Click to see Annotation Detail View

  
Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
FCGR3AHumanglomerulonephritis susceptibilityIAGP associated with Lupus Erythematosus more ...RGD 
Fcgr3aRatglomerulonephritis susceptibilityISOFCGR3A (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
Fcgr4Mouseglomerulonephritis susceptibilityISOFCGR3A (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
FCGR2AHumanlymphopenia susceptibilityIAGP associated with Lupus Erythematosus more ...RGD 
FCGR3AHumanlymphopenia susceptibilityIAGP associated with Lupus Erythematosus more ...RGD 
Fcgr2aRatlymphopenia susceptibilityISOFCGR2A (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
Fcgr3Mouselymphopenia susceptibilityISOFCGR2A (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
Fcgr3aRatlymphopenia susceptibilityISOFCGR3A (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
Fcgr4Mouselymphopenia susceptibilityISOFCGR3A (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
IL1RNHumanSerositis susceptibilityIAGP associated with Lupus Erythematosus more ...RGD 
Il1rnRatSerositis susceptibilityISOIL1RN (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
Il1rnMouseSerositis susceptibilityISOIL1RN (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
FCGR2AHumanvisual epilepsy susceptibilityIAGP associated with Lupus Erythematosus more ...RGD 
FCGR3AHumanvisual epilepsy susceptibilityIAGP associated with Lupus Erythematosus more ...RGD 
Fcgr2aRatvisual epilepsy susceptibilityISOFCGR2A (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
Fcgr3Mousevisual epilepsy susceptibilityISOFCGR2A (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
Fcgr3aRatvisual epilepsy susceptibilityISOFCGR3A (Homo sapiens)associated with Lupus Erythematosus more ...RGD 
Fcgr4Mousevisual epilepsy susceptibilityISOFCGR3A (Homo sapiens)associated with Lupus Erythematosus more ...RGD 

Phenotype Annotations    Click to see Annotation Detail View

Manual Human Phenotype Annotations - RGD

Object SymbolSpeciesTermQualifierEvidenceWithNotesSourceOriginal Reference(s)
IL1RNHumanIncreased inflammatory response susceptibilityIAGP associated with Lupus Erythematosus more ...RGD 
Objects Annotated

Genes (Rattus norvegicus)
Fcgr2a  (Fc gamma receptor 2A)
Fcgr3a  (Fc gamma receptor 3A)
Il1rn  (interleukin 1 receptor antagonist)

Genes (Mus musculus)
Fcgr3  (Fc receptor, IgG, low affinity III)
Fcgr4  (Fc receptor, IgG, low affinity IV)
Il1rn  (interleukin 1 receptor antagonist)

Genes (Homo sapiens)
FCGR2A  (Fc gamma receptor IIa)
FCGR3A  (Fc gamma receptor IIIa)
IL1RN  (interleukin 1 receptor antagonist)


Additional Information