C4A deficiency due to a 2 bp insertion is increased in patients with systemic lupus erythematosus

Objective. The association of C4A deficiency with systemic lupus erythemato sus (SLE) is well documented. In Caucasian populations, the most common cau se of C4A deficiency is a large gene deletion in linkage disequilibrium wit h a conserved MHC haplotype. Because of this linkage disequilibrium, it has been difficult to determine which of the genes constitutes the disease sus ceptibility allele. Evidence from non-caucasoid populations has supported a role for C4A deficiency in SLE. We investigated whether a specific genetic cause of C4A deficiency, not associated with A1, B8, DR3, is found with in creased frequency in SLE compared to controls. Methods. Polymerase chain reaction was used to identify carriers of a 2 bas e pair (bp) insertion in exon 29. In total, 188 patients with SLE from the Johns Hopkins lupus cohort and 222 controls were genotyped. Results. The 2 bp insertion was found more frequently in patients with SLE compared to controls and was more common in Caucasian than in African Ameri can SLE patients. There were no clinical differences between patients that carried the mutation and those that did not. Conclusion. The association of this C4A null allele with SLE supports a rol e fur C4A deficiency independent of other MHC associations in the etiopatho genesis of SLE.