HLA and hypocomplementemia: the disadvantage of carrying the HLA-B35 and the silent alleles of the C4 complement component.
Hypocomplementemia is an extremely complex phenomenon: we devoted our attention to its immunogenetic basis, particularly to the HLA haplotypes involved and to the study of C4 polymorphic genes. With this in mind we analyzed a group of unrelated patients with hypocomplementemia and 15 families suffering from specific C4 deficiency. Firstly, we performed a population analysis in order to identify a statistically significant association: HLA-B35 and C4BQ0 alleles, in the total group of hypocomplementemic individuals, seem to be associated with the primary disease. Secondly, we defined HLA haplotypes clear-cut segregation in the hypocomplementemic families and we identified the most common HLA haplotypes carrying B35 and C4 null allele associated with this condition. With the aid of correspondence analysis and the Transmission Disequilibrium Test (TDT), we measured the strength of this association. In this work, mainly through family analysis, we envisaged a potentially interesting genomic trait, within HLA, close to B locus, that seems to be involved in hypocomplementemia itself and perhaps in hypocomplementemia-related disorders.
Laboratorio di Biochimica e Genetica, Clinica Malattie Respiratorie, IRCCS Policlinico S.Matteo, Universitá di Pavia, Italy.
M
M
Zorzetto
G
G
Ricevuti
M
M
Martinetti
D
D
Gritti
C
C
Gasparetto
A
A
De Silvestri
L
L
Salvaneschi
M
M
Cuccia
D000465:Algorithms; D000483:Alleles; D015153:Blotting, Western; D003181:Complement C4 / Q000235:genetics* / Q000378:metabolism*; D011415:Complement Factor B / Q000378:metabolism; D003165:Complement System Proteins / Q000172:deficiency* / Q000235:genetics*; D003720:Densitometry; D004591:Electrophoresis, Polyacrylamide Gel; D005190:Family; D005787:Gene Frequency; D008040:Genetic Linkage / Q000235:genetics; D006680:HLA Antigens / Q000235:genetics*; D015797:HLA-B35 Antigen / Q000235:genetics* / Q000378:metabolism*; D006239:Haplotypes; D006801:Humans; D008126:Lod Score; D011110:Polymorphism, Genetic / Q000235:genetics; D011153:Population
D003181:Complement C4; D006680:HLA Antigens; D015797:HLA-B35 Antigen; D003165:Complement System Proteins; D011415:Complement Factor B