title: Analysis of C1q polymorphisms suggests association with systemic lupus erythematosus, serum C1q and CH50 levels and disease severity.
abstract: BACKGROUND
  Several findings link systemic lupus erythematosus (SLE) with C1q, the first molecule of the classical complement pathway. Polymorphisms of the C1qA gene are associated with low serum C1q levels in patients with cutaneous LE, but C1q polymorphisms have not been studied in patients with systemic lupus.
  
  
  OBJECTIVE
  To determine whether polymorphisms of the C1q genes are associated with SLE, disease phenotypes, serum C1q and CH50 levels.
  
  
  METHODS
  DNA for genetic analysis was obtained from 103 Caucasian patients with SLE and their family members. Five tag single nucleotide polymorphisms (tag SNPs) served as unique markers for underlying SNPs in the genes of the C1q protein. The pedigree disequilibrium test (PDT) was applied to trios to determine association of markers with SLE, SLE phenotypes, low serum C1q and low CH50. Single SNP association and haplotype analysis was also performed.
  
  
  RESULTS
  The PDT revealed a significant association of the tag SNP rs631090 (covering the C1qB gene) with SLE (p = 0.02). Rs631090 was moderately associated with low serum C1q levels (p = 0.06). In addition, the tag SNPs rs292001 and rs294183 were associated with more severe SLE (Systemic Lupus Erythematosus International Collaborating Clinics (SLICC) damage index score>0; p = 0.007 and p = 0.02, respectively). Haplotype analysis and single SNP association analysis showed no significant associations, but additional analyses revealed that marker rs587585 is associated with low serum C1q and CH50 levels.
  
  
  CONCLUSIONS
  C1q polymorphisms are associated with SLE, serum C1q and CH50 levels in a stable founder population of patients with SLE. Although the studied population was small and allele frequencies were low, this is the first study to suggest an association of C1q polymorphisms with SLE.
authors.affiliation: Department of Rheumatology and Clinical Immunology, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands. h.a.martens@int.umcg.nl
authors.forename: H A
authors.initials: HA
authors.lastname: Martens
authors.forename: M W
authors.initials: MW
authors.lastname: Zuurman
authors.forename: A H M
authors.initials: AH
authors.lastname: de Lange
authors.forename: I M
authors.initials: IM
authors.lastname: Nolte
authors.forename: G
authors.initials: G
authors.lastname: van der Steege
authors.forename: G J
authors.initials: GJ
authors.lastname: Navis
authors.forename: C G M
authors.initials: CG
authors.lastname: Kallenberg
authors.forename: M A
authors.initials: MA
authors.lastname: Seelen
authors.forename: M
authors.initials: M
authors.lastname: Bijl
mesh_terms: D000328:Adult; D000368:Aged; D002878:Chromosomes, Human, Pair 1 / Q000235:genetics; D015922:Complement C1q / Q000032:analysis / Q000235:genetics*; D015941:Complement Hemolytic Activity Assay; D003171:Complement Pathway, Classical; D005260:Female; D020022:Genetic Predisposition to Disease; D006239:Haplotypes; D006801:Humans; D015810:Linkage Disequilibrium; D008180:Lupus Erythematosus, Systemic / Q000235:genetics* / Q000276:immunology; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D012720:Severity of Illness Index; D055815:Young Adult
chemical_list: D015922:Complement C1q