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

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 CIQA gene. We also describe an association between this SNP and lower levels of serum Clq. 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 ClQA gene. We have designated this SNP ClqA-Gly70(GGA) (the GenBank sequence at this location is ClqA-G1y70(GGG)). A survey of 19 SCLE patients showed that 11 (58%) were homozygous for ClqA-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 ClqA-Gly70GGA SNP, 41 (66%) controls were heterozygous and eight (13%) controls were homozygous for the GenBank sequence. Thus, the ClqA-Gly70(GGA) 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 Clq expression since its presence correlates inversely with serum levels of Clq antigenic protein in both SCLE patients and normal controls. The mechanism by which this phenotypic change is associated with the translationally silent (synonymous) ClqA-Gly70GGA genetic variation is currently unknown.