Background: Several findings link systemic lupus erythematosus (SLE) with C1q. 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 systemic lupus patients.
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 SLE patients 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, tag-SNP’s rs292001 and rs294183 were associated with more severe SLE (SLICC 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.
Conclusion: C1q polymorphisms are associated with SLE, serum C1q and CH50 levels in a stable founder population of SLE patients. 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.