Cq1 Exon Polymorphisms in Caucasian and African American Systemic Lupus Erythematosus patients

Abstract Background: C1q protein is composed of three protein chains (A, B, and C) that are the products of separate genes. Genetic deficiencies in C1q are important factors influencing the risk of systemic lupus erythematosus (SLE). Therefore, this study aimed to investigate the possible association of single nucleotide polymorphisms (SNPs) in the coding region of the C1q genes with SLE. Methods: Initially, the encoding regions of C1q A, B, and C chains were amplified and directly sequenced from leukocyte DNA from a subset of Caucasian and African American SLE patients and healthy controls. Results: Three synonymous single SNPs were identified: nucleotide 276G>A in C1qA, 66C>A in C1qB, and 129G>A in C1qC. To test if any of these SNPs were linked to susceptibility to SLE, they were measured in 210 SLE patients (151 African Americans and 59 Caucasians) and 129 matched healthy controls (55 African Americans and 74 Caucasians) by restriction fragment length polymorphism (RFLP) analysis. Statistically, no differences were found in genotype or allele frequencies between patients and controls for the 276G>A or 66C>A SNP. However, in Caucasians, the frequencies of the 129G>A genotypes were different between SLE patients and controls (P = 0.005), specifically with the GG genotype being overrepresented in the controls (P = 0.004). Conclusion: Our results show that the homozygous 129GG genotype is associated with protection against SLE onset. This protection is race dependent, being observed in Caucasians but not African Americans. The mechanism of this association is currently unclear.