Advanced

Association between SLE nephritis and polymorphic variants of the CRP and Fc gamma RIIIa genes

Jönsen, Andreas LU ; Gunnarsson, I.; Gullstrand, Birgitta LU ; Svenungsson, E.; Bengtsson, Anders LU ; Nived, Ola LU ; Lundberg, I. E.; Truedsson, Lennart LU and Sturfelt, Gunnar LU (2007) In Rheumatology 46(9). p.1417-1421
Abstract
Objectives. To study the relationship between clinical manifestations in systemic lupus erythematosus (SLE) with polymorphisms in suggested susceptibility genes encoding Fc gamma RIIa, Fc gamma RIIIa, Fc gamma RIIIb, 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... (More)
Objectives. To study the relationship between clinical manifestations in systemic lupus erythematosus (SLE) with polymorphisms in suggested susceptibility genes encoding Fc gamma RIIa, Fc gamma RIIIa, Fc gamma RIIIb, 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 Fc gamma RIIIa 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 Fc gamma RIIIb NA2/NA2 genotype was associated with butterfly rash (P< 0.01). An association was found between seizures and the presence of both the Fc gamma RIIa R/R and the Fc gamma RIIIa 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 Fc gamma RIIa R/R genotype and CRP4 A-allele was associated with lymphopenia (P= 0.02) and a similar result was found for the combination of Fc gamma RIIIa F/F and Fc gamma RIIIb NA2/NA2 (P= 0.04). Conclusions. Polymorphic variants of the CRP and Fc gamma-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. (Less)
Please use this url to cite or link to this publication:
author
organization
publishing date
type
Contribution to journal
publication status
published
subject
keywords
polymorphism, genetic, Fc receptor, systemic lupus erythematosus, C-reactive protein, glomerulonephritis
in
Rheumatology
volume
46
issue
9
pages
1417 - 1421
publisher
Oxford University Press
external identifiers
  • wos:000249561000007
  • scopus:34548280426
ISSN
1462-0332
DOI
10.1093/rheumatology/kem167
language
English
LU publication?
yes
id
69e595f1-1c48-4ef9-a046-9194ae194bd8 (old id 656384)
alternative location
http://www.ncbi.nlm.nih.gov/entrez/query.fcgi?cmd=Retrieve&db=PubMed&list_uids=17596285&dopt=Abstract
date added to LUP
2007-12-13 14:05:36
date last changed
2017-08-13 04:31:18
@article{69e595f1-1c48-4ef9-a046-9194ae194bd8,
  abstract     = {Objectives. To study the relationship between clinical manifestations in systemic lupus erythematosus (SLE) with polymorphisms in suggested susceptibility genes encoding Fc gamma RIIa, Fc gamma RIIIa, Fc gamma RIIIb, 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&lt; 0.01) and inversely correlated with arthritis (P &lt; 0.01), when comparing within the SLE group. The Fc gamma RIIIa 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&lt;0.001). Furthermore, the Fc gamma RIIIb NA2/NA2 genotype was associated with butterfly rash (P&lt; 0.01). An association was found between seizures and the presence of both the Fc gamma RIIa R/R and the Fc gamma RIIIa F/F genotypes (P&lt; 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 Fc gamma RIIa R/R genotype and CRP4 A-allele was associated with lymphopenia (P= 0.02) and a similar result was found for the combination of Fc gamma RIIIa F/F and Fc gamma RIIIb NA2/NA2 (P= 0.04). Conclusions. Polymorphic variants of the CRP and Fc gamma-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.},
  author       = {Jönsen, Andreas and Gunnarsson, I. and Gullstrand, Birgitta and Svenungsson, E. and Bengtsson, Anders and Nived, Ola and Lundberg, I. E. and Truedsson, Lennart and Sturfelt, Gunnar},
  issn         = {1462-0332},
  keyword      = {polymorphism,genetic,Fc receptor,systemic lupus erythematosus,C-reactive protein,glomerulonephritis},
  language     = {eng},
  number       = {9},
  pages        = {1417--1421},
  publisher    = {Oxford University Press},
  series       = {Rheumatology},
  title        = {Association between SLE nephritis and polymorphic variants of the CRP and Fc gamma RIIIa genes},
  url          = {http://dx.doi.org/10.1093/rheumatology/kem167},
  volume       = {46},
  year         = {2007},
}