A study of the genetic basis of C4A protein deficiency. Detection of C4A gene deletion by long-range PCR and its associated haplotypes

Abstract

Objective: To study the frequency of a C4A gene deletions as the genetic basis of C4A protein deficiency (C4AQ0) and its associated haplotypes in Icelandic families with systemic lupus erythematosus (SLE). Methods: Nine multiplex SLE families were genotyped for C4A gene deletions using a long-range polymerase chain reaction (LR-PCR) method, and major histocompatibility complex (MHC) haplotypes were defined. Results: Of the SLE patients, first-degree and second-degree relatives, 53.8%, 47.9%, and 28.6% had C4AQ0, respectively. A C4A gene deletion was found to be the genetic basis for C4AQ0 in 64.3% of SLE patients, 60.0% of first-degree and 50.0% of second-degree relatives. All individuals carrying haplotype B8-C4AQ0-C4B1-DR3 had a deletion, and the deletion was also found on haplotypes B8-C4AQ0-C4B1-DR7 and B7-C4AQ0-C4B1-DR3. Conclusion: The study shows that a C4A gene deletion is the most common genetic basis for C4AQ0. It accounts for two-thirds of C4AQ0 and is found on different MHC haplotypes. One-third of C4AQ0 is due to other as yet undefined genetic changes. The results demonstrate a heterogeneous genetic background for C4AQ0, giving further support for the hypothesis that C4AQ0 may be an independent risk factor for SLE.