Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0024141 (systemic lupus erythematosus)
 44,322 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The molecular basis of complement component C4A deficiency in white U.S. and Mexican patients with systemic lupus erythematosus (SLE) was studied. Genomic DNA from SLE patients and non-SLE controls was analyzed for restriction fragments using HindIII and a 5' C4 cDNA probe. C4A gene deletion was recognized by the loss of a 15-kb restriction fragment and the appearance of a 8.5-kb fragment. Thirty-two selected U.S. SLE patients, 7 nonSLE controls, and 11 Mexican SLE patients and 9 relatives were studied. The deletion was recognized in all of the 14 HLA-B8;DR3 SLE patients with a C4A protein deficiency. Two SLE patients with DR3 but without B8 also had this gene deletion. None of the 3 U.S. SLE nonDR3, C4A protein deficient patients nor 20 C4A protein deficient Mexican individuals (11 SLE patients and 9 relatives; none had B8 and/or DR3) showed this deletion. Thus the C4A gene deletion failed to account for the C4A protein deficiency in all the nonDR3 Mexicans and in some U.S. SLE patients. To determine whether gene conversion at the C4A locus would encode a C4B-like protein and be responsible for the C4A protein deficiency (in nonDR3 patients), the C4d region of the gene was amplified by polymerase chain reaction and subjected to Nla IV digestion, and restriction fragment analysis was performed using a C4d region-specific probe. The resulting restriction fragment length polymorphism pattern revealed no changes in the isotype-specific region of the gene as characterized by C4A-specific 276- and 191-bp fragments in Dr3 or nonDR3 individuals. Thus, homoexpression of C4B at both loci was not responsible for C4A deficiency in nonDR3 SLE patients without C4A gene deletion.
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PMID:DR3 and nonDR3 associated complement component C4A deficiency in systemic lupus erythematosus. 204 37

HLA-A, -B and -DR gene frequency distributions in populations of Australia, Melanesia, Micronesia and Polynesia are examined in relationship to known HLA and disease associations in other populations. With the exception of a correlation between Reiter's syndrome and B27, other HLA and disease associations are markedly absent. Recombinant DNA and cellular subtyping analyses suggest that the HLA-DR subtypes predominating in susceptibility to several autoimmune disorders in Caucasoids are rare in Oceania. The high frequency of serum complement component C4A deficiency in Australian Aborigines may explain the high prevalence of systemic lupus erythematosus in this group.
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PMID:HLA and disease in Oceania. 269 21

A high frequency of serum complement component C4A deficiency may explain the higher prevalence and greater severity of systemic lupus erythematosus reported in Australian Aborigines. Inherited deficiencies of serum complement components C4A, C4B, and C2 were examined in two Australian Aboriginal populations from Darwin and Alice Springs and compared with the prevalence of complement deficiencies in white Australian blood donors. The frequency of C4A deficiency alleles was 29% in Darwin Aborigines compared with 12% in Alice Springs and 17% in Canberra blood donors. Partial C4B deficiency was also higher in Darwin Aborigines than in the other populations. Inherited deficiency of serum complement component C2 was not observed.
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PMID:A high frequency of inherited deficiency of complement component C4 in Darwin Aborigines. 350 12

C4A null alleles (C4AQ0) have an increased frequency in SLE patients. Surprisingly some of them have no detectable gene deletion. In order to characterize the level of the defect in such patients, we used a RT-PCR/nested PCR technique and detected the presence of C4A mRNA in normal amounts. Since maturation abnormalities are almost always accompanied by a decrease in mRNA concentration, this result suggests that the defect may be located at the translational level.
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PMID:Study of C4A mRNA in mononuclear blood cells from a patient with SLE and C4A homozygous deficiency without C4A gene deletion. 789 2

Although a heterozygous deficiency of either complement component C4A or C4B is common, and each has a frequency of approximately 20% in a Caucasian population, complete deficiencies of both C4A and C4B proteins are extremely rare. In this paper the clinical courses for seven complete C4 deficiency patients are described in detail, and the molecular defects for complete C4 deficiencies are elucidated. Three patients with homozygous HLA A24 Cw7 B38 DR13 had systemic lupus erythematosus, mesangial glomerulonephritis, and severe skin lesions or membranous nephropathy. Immunofixation, genomic restriction fragment length polymorphisms, and pulsed field gel electrophoresis experiments revealed the presence of monomodular RP-C4-CYP21-TNX (RCCX) modules, each containing a solitary, long C4A mutant gene. Sequencing of the mutant C4A genes revealed a 2-bp, GT deletion in exon 13 that leads to protein truncation. The other four patients with homozygous HLA A30 B18 DR7 had SLE, severe kidney disorders including mesangial or membranoproliferative glomerulonephritis, and/or Henoch Schoenlein purpura. Molecular genetic analyses revealed an unusual RCCX structure with two short C4B mutant genes, each followed by an intact gene for steroid 21-hydroxylase. Nine identical, intronic mutations were found in each mutant C4B. In particular, the 8127 g-->a mutation present at the donor site of intron 28 may cause an RNA splice defect. Analyses of 12 complete C4 deficiency patients revealed two hot spots of deleterious mutations: one is located at exon 13, the others within a 2.6-kb genomic region spanning exons 20-29. Screening of these mutations may facilitate epidemiologic studies of C4 in infectious, autoimmune, and kidney diseases.
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PMID:Complete complement components C4A and C4B deficiencies in human kidney diseases and systemic lupus erythematosus. 1529 99