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Mutations in genes encoding complement inhibitors CD46 and CFH affect the age at nephritis onset in patients with systemic lupus erythematosus

Jönsen, Andreas LU ; Nilsson, Sara LU ; Ahlqvist, Emma LU ; Svenungsson, Elisabet; Gunnarsson, Iva; Eriksson, Karin G.; Bengtsson, Anders LU ; Zickert, Agneta; Eloranta, Maija-Leena and Truedsson, Lennart LU , et al. (2011) In Arthritis Research and Therapy 13(6).
Abstract
Introduction: Inherited deficiencies of several complement components strongly predispose to systemic lupus erythematosus (SLE) while deficiencies of complement inhibitors are found in kidney diseases such as atypical hemolytic uremic syndrome (aHUS). Methods: The exons of complement inhibitor genes CD46 and CFH (factor H) were fully sequenced using the Sanger method in SLE patients with nephritis originating from two cohorts from southern and mid Sweden (n = 196). All identified mutations and polymorphisms were then analyzed in SLE patients without nephritis (n = 326) and in healthy controls (n = 523). Results: We found nonsynonymous, heterozygous mutations in CFH in 6.1% patients with nephritis, in comparison with 4.0% and 5.4% in... (More)
Introduction: Inherited deficiencies of several complement components strongly predispose to systemic lupus erythematosus (SLE) while deficiencies of complement inhibitors are found in kidney diseases such as atypical hemolytic uremic syndrome (aHUS). Methods: The exons of complement inhibitor genes CD46 and CFH (factor H) were fully sequenced using the Sanger method in SLE patients with nephritis originating from two cohorts from southern and mid Sweden (n = 196). All identified mutations and polymorphisms were then analyzed in SLE patients without nephritis (n = 326) and in healthy controls (n = 523). Results: We found nonsynonymous, heterozygous mutations in CFH in 6.1% patients with nephritis, in comparison with 4.0% and 5.4% in patients without nephritis and controls, respectively. No associations of SLE or nephritis with common variants in CFH (V62I/Y402H/E936D) were found. Furthermore, we found two nonsynonymous heterozygous mutations in CD46 in SLE patients but not in controls. The A353V polymorphism, known to affect function of CD46, was found in 6.6% of nephritis patients versus 4.9% and 6.1% of the non-nephritis SLE patients and controls. The presence of mutations in CD46 and CFH did not predispose to SLE or nephritis but was associated with earlier onset of nephritis. Furthermore, we found weak indications that there is one protective and one risk haplotype predisposing to nephritis composed of several polymorphisms in noncoding regions of CD46, which were previously implicated in aHUS. Conclusions: SLE nephritis is not associated with frequent mutations in CFH and CD46 as found in aHUS but these may be modifying factors causing earlier onset of nephritis. (Less)
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Arthritis Research and Therapy
volume
13
issue
6
publisher
BioMed Central
external identifiers
  • wos:000301175700026
  • scopus:84855765646
ISSN
1478-6362
DOI
10.1186/ar3539
language
English
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yes
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c1d67dd1-64a7-46cc-8bfb-9567447a5ae5 (old id 2493692)
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2012-05-08 08:31:50
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2017-09-17 03:48:33
@article{c1d67dd1-64a7-46cc-8bfb-9567447a5ae5,
  abstract     = {Introduction: Inherited deficiencies of several complement components strongly predispose to systemic lupus erythematosus (SLE) while deficiencies of complement inhibitors are found in kidney diseases such as atypical hemolytic uremic syndrome (aHUS). Methods: The exons of complement inhibitor genes CD46 and CFH (factor H) were fully sequenced using the Sanger method in SLE patients with nephritis originating from two cohorts from southern and mid Sweden (n = 196). All identified mutations and polymorphisms were then analyzed in SLE patients without nephritis (n = 326) and in healthy controls (n = 523). Results: We found nonsynonymous, heterozygous mutations in CFH in 6.1% patients with nephritis, in comparison with 4.0% and 5.4% in patients without nephritis and controls, respectively. No associations of SLE or nephritis with common variants in CFH (V62I/Y402H/E936D) were found. Furthermore, we found two nonsynonymous heterozygous mutations in CD46 in SLE patients but not in controls. The A353V polymorphism, known to affect function of CD46, was found in 6.6% of nephritis patients versus 4.9% and 6.1% of the non-nephritis SLE patients and controls. The presence of mutations in CD46 and CFH did not predispose to SLE or nephritis but was associated with earlier onset of nephritis. Furthermore, we found weak indications that there is one protective and one risk haplotype predisposing to nephritis composed of several polymorphisms in noncoding regions of CD46, which were previously implicated in aHUS. Conclusions: SLE nephritis is not associated with frequent mutations in CFH and CD46 as found in aHUS but these may be modifying factors causing earlier onset of nephritis.},
  articleno    = {R206},
  author       = {Jönsen, Andreas and Nilsson, Sara and Ahlqvist, Emma and Svenungsson, Elisabet and Gunnarsson, Iva and Eriksson, Karin G. and Bengtsson, Anders and Zickert, Agneta and Eloranta, Maija-Leena and Truedsson, Lennart and Ronnblom, Lars and Nordmark, Gunnel and Sturfelt, Gunnar and Blom, Anna},
  issn         = {1478-6362},
  language     = {eng},
  number       = {6},
  publisher    = {BioMed Central},
  series       = {Arthritis Research and Therapy},
  title        = {Mutations in genes encoding complement inhibitors CD46 and CFH affect the age at nephritis onset in patients with systemic lupus erythematosus},
  url          = {http://dx.doi.org/10.1186/ar3539},
  volume       = {13},
  year         = {2011},
}