Molecular heterogeneity of complement component C4-null and 21-hydroxylase genes in systemic lupus erythematosus.
C4A-null alleles (C4A*Q0) and hereditary complete C4 deficiency (homozygous C4A*Q0,C4B*Q0) are associated with systemic lupus erythematosus (SLE). Using Southern blot analysis with C4 and 21-hydroxylase (21-OH) DNA probes, we studied SLE patients and normal control subjects with or without C4A*Q0, and 2 C4-deficient SLE patients. A previously reported large C4A,21-OHA gene deletion associated in normal subjects with the HLA-A1;B8;DR3;C4AQ0 haplotype was detected by the appearance of a new C4 Hind III 8.5-kb fragment and disappearance of a 3.2-kb 21-OH Taq I fragment. In 3 SLE patients with homozygous C4A*Q0 and 15 with heterozygous C4A*Q0, this deletion pattern occurred almost exclusively in association with the HLA-B8;DR3;C4A*Q0 phenotype; the one exception was a black SLE patient. Other C4A*Q0-bearing HLA phenotypes in white patients and black patients with SLE, and the 2 completely C4-deficient SLE patients, had normal DNA hybridization to both C4 and 21-OH probes. The genetic basis for C4-null alleles in SLE is heterogeneous. A large C4A,21-OHA deletion occurs mainly on the HLA-B8;DR3;C4AQ0 haplotype in SLE and controls. Other HLA haplotypes bearing C4A*Q0 have normal C4 and 21-OH genes, as demonstrated by Southern blot analysis.
Goldstein
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Department of Internal Medicine, University of Texas Health Science Center, Houston 77030.
Arnett
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McLean
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Bias
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Duvic
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D000483:Alleles; D044383:Black People; D003181:Complement C4 / Q000172:deficiency / Q000235:genetics*; D005796:Genes; D006680:HLA Antigens / Q000145:classification; D006579:Heterozygote; D006801:Humans; D008180:Lupus Erythematosus, Systemic / Q000150:complications / Q000235:genetics*; D008967:Molecular Biology; D013255:Steroid 21-Hydroxylase / Q000235:genetics*; D013250:Steroid Hydroxylases / Q000235:genetics*; D044465:White People
D003181:Complement C4; D006680:HLA Antigens; D013250:Steroid Hydroxylases; D013255:Steroid 21-Hydroxylase