Major-histocompatibility-complex extended haplotypes in membranoproliferative glomerulonephritis.
Membranoproliferative glomerulonephritis is often associated with evidence of immune derangement, especially hypocomplementemia. We studied genetic markers for membranoproliferative glomerulonephritis within the major histocompatibility complex in 34 patients and their families and in 29 normal families. We examined the frequencies of extended haplotypes (combinations of alleles that tend to occur together) in patients and controls. The extended haplotype HLA-B8,DR3,SC01,GLO2(glyoxalase I 2) was observed in 9 of 68 disease-associated haplotypes (13 percent), but in only 3 of 205 controls (1 percent) (relative risk, 14.79; P less than 0.001). An extended haplotype similar except for a different glyoxalase allotype (B8,DR3,SC01,GLO1) did not occur with increased frequency, nor did any other extended haplotypes. Patients with the extended haplotype B8,DR3,SC01,GLO2 had a higher incidence of renal insufficiency than those without it (P less than 0.01). The data support the hypothesis that a specific extended haplotype of the major histocompatibility complex is associated with susceptibility to membranoproliferative glomerulonephritis, and that patients with glomerulonephritis who have this extended haplotype have a poorer prognosis for kidney survival than those without the haplotype.
Welch
T R
TR
Beischel
L
L
Balakrishnan
K
K
Quinlan
M
M
West
C D
CD
D000483:Alleles; D003175:Complement C2 / Q000235:genetics; D003181:Complement C4 / Q000235:genetics; D011415:Complement Factor B / Q000235:genetics; D005260:Female; D005787:Gene Frequency; D005921:Glomerulonephritis / Q000235:genetics* / Q000276:immunology / Q000401:mortality; D006680:HLA Antigens / Q000235:genetics; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II / Q000235:genetics; D006801:Humans; D007791:Lactoylglutathione Lyase / Q000235:genetics; D008285:Major Histocompatibility Complex; D008297:Male; D011110:Polymorphism, Genetic; D011379:Prognosis
D003175:Complement C2; D003181:Complement C4; D006680:HLA Antigens; D006684:HLA-DR Antigens; D000949:Histocompatibility Antigens Class II; D011415:Complement Factor B; D007791:Lactoylglutathione Lyase