Genetic study on HLA class II and class III region in the disease associated with IgA nephropathy.
Increased frequency of C4 gene deletions in IgA nephropathy and Henoch-Schönlein purpura nephritis. To determine the frequency of complement 4 (C4) deficiency among the patients with IgA nephropathy (IgAN) and Henoch-Schönlein purpura nephritis (HSPN), C4 and factor B protein allotypes and the DNA restriction fragment length polymorphism (RFLP) of C4, steroid 21-hydroxylase (21OHase), HLA DQ beta and DR beta chain genes were studied. Genomic DNA from 32 patients with IgAN, 24 patients with HSPN and 143 controls was digested with restriction enzyme TaqI or BamHI and subjected to Southern analysis. The frequency of C4 gene deletions was significantly increased in the patients (16.1 vs. 2.8%, p = 0.002). The serum C4 concentration in patients with C4 gene deletion was significantly lower than in patients without gene deletion (11.4 +/- 2.4 vs. 19.7 +/- 5.2 mg/dl, p = 0.001). DNA-RFLP typing of DQB/BamHI and DRB/TaqI showed increased frequency of 10.26 kb of D-DQw4/8/9 (87.5 vs. 64.5%, p = 0.004) and 5.22 kb of D-DR4 (66.1 vs. 41.7%, p = 0.03) among the patients. Segregation analysis showed that the association of the D-DQw4/8/9 and D-DR4 with the diseases was not responsible for the increased frequency of C4 gene deletion in the patients. The decreased concentration of C4 in sera in C4 gene-deleted patients might be directly involved in the pathogenesis of IgAN and HSPN.
Abe
J
J
Department of Immunology, National Children's Hospital Medical Research Center, Tokyo, Japan.
Kohsaka
T
T
Tanaka
M
M
Kobayashi
N
N
D002648:Child; D003181:Complement C4 / Q000172:deficiency / Q000235:genetics; D005260:Female; D017353:Gene Deletion; D005787:Gene Frequency; D005922:Glomerulonephritis, IGA / Q000235:genetics* / Q000276:immunology*; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006801:Humans; D011695:IgA Vasculitis / Q000235:genetics* / Q000276:immunology*; D008297:Male; D010375:Pedigree; D012150:Polymorphism, Restriction Fragment Length
D003181:Complement C4; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens