title: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Centre for Rheumatology Research, Landspítali University Hospital, Reykjavík, Iceland.
authors.forename: H
authors.initials: H
authors.lastname: Kristjánsdóttir
authors.forename: K
authors.initials: K
authors.lastname: Steinsson
mesh_terms: D017677:Age Distribution; D001483:Base Sequence; D015331:Cohort Studies; D015934:Complement C4a / Q000235:genetics*; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006239:Haplotypes / Q000235:genetics*; D006579:Heterozygote; D006801:Humans; D007055:Iceland / Q000453:epidemiology; D015994:Incidence; D008180:Lupus Erythematosus, Systemic / Q000175:diagnosis / Q000453:epidemiology* / Q000235:genetics*; D008297:Male; D008969:Molecular Sequence Data; D010375:Pedigree; D016133:Polymerase Chain Reaction; D012720:Severity of Illness Index; D017678:Sex Distribution
chemical_list: D015934:Complement C4a