Homozygous single nucleotide polymorphism of the complement C1QA gene is associated with decreased levels of C1q in patients with subacute cutaneous lupus erythematosus

• Published in: Lupus Vol. 12; no. 2; pp. 124 - 132
• Main Authors: Racila, D M, Sontheimer, C J, Sheffield, A, Wisnieski, J J, Racila, E, Sontheimer, R D
• Format: Journal Article
• Language: English
• Published: Thousand Oaks, CA Sage Publications 2003; Sage Publications Ltd
• Subjects: Amino acids; Base Sequence - genetics; Complement C1q - genetics; Dermatology; Female; Haplotypes; Homozygote; Hospitals; Humans; Lupus; Lupus Erythematosus, Cutaneous - genetics; Male; Pathogenesis; Polymorphism; Polymorphism, Single Nucleotide - genetics; Skin diseases; White people; United States > US; Iowa City Iowa; Indianapolis Indiana; photosensitivity disorders; genetics; complement; single nucleotide polymorphism; lupus
• DOI: 10.1191/0961203303lu329oa
• EISSN: 1477-0962
• ISSN: 0961-2033

We report an association between a non-familial form of photosensitive Lupus-specific skin disease, subacute cutaneous lupus erythematosus (SCLE), and a new single nucleotide polymorphism (SNP) in the C1QA gene. We also describe an association between this SNP and lower levels of serum C1q. This SNP consists of adenine replacing the third guanine in the codon for amino acid residue Gly70 (position excludes the 22 amino acid leading peptide) that is located in the second exon of the C1QA gene. We have designated this SNP C1qA - Gly70GGA (the GenBank sequence at this location is C1qA - Gly70GGG). A survey of 19 SCLE patients showed that 11 (58%) were homozygous for C1qA - Gly70GGA SNP, seven (37%) were heterozygous, and only one patient (5%) was homozygous for the GenBank sequence. In contrast, only 13 of 62 (21%) normal controls were homozygous for the C1qA - Gly70GGA SNP, 41 (66%) controls were heterozygous and eight (13%) controls were homozygous for the GenBank sequence. Thus, the C1qA - Gly70GGA SNP is strongly associated with SCLE (P-value = 0.005 by chi-square analysis with Yates correction). This SNP would traditionally be classified as clinically silent as it does not encode a different amino acid. However, our studies have suggested that this SNP appears to be associated with a functional abnormality of C1q expression since its presence correlates inversely with serum levels of C1q antigenic protein in both SCLE patients and normal controls. The mechanism by which this phenotypic change is associated with the translationally silent (synonymous) C1qA - Gly70GGA genetic variation is currently unknown.