Molecular analysis of HLA-DQB1 alleles in childhood common acute lymphoblastic leukaemia.
Epidemiological studies suggest that childhood common acute lymphoblastic leukaemia (c-ALL) may be the rare outcome of early post-natal infection with a common infectious agent.
One of the factors that may determine whether a child succumbs to c-ALL is how it responds to the candidate infection.
Since immune responses to infection are under the partial control of (human leucocyte antigen) HLA genes, an association between an HLA allele and c-ALL could provide support for an infectious aetiology.
To define the limit of c-ALL susceptibility within the HLA region, we have compared HLA-DQB1 allele frequencies in a cohort of 62 children with c-ALL with 76 newborn controls, using group-specific polymerase chain reaction (PCR) amplification, and single-strand conformation polymorphism (SSCP) analysis.
We find that a significant excess of children with c-ALL type for DQB1*05 epsilonrelative risk (RR) : 2.54, uncorrected P=0.038zêta, and a marginal excess with DQB1*0501 (RR : 2.18 ; P=0.095).
Only 3 of the 62 children with c-ALL have the other susceptibility allele, DPB1*0201 as well as DQB1*0501, whereas 15 had one or the other allele.
This suggests that HLA-associated susceptibility may be determined independently by at least two loci, and is not due to linkage disequilibrium.
The combined relative risk of the two groups of children with DPB1*0201 and/or DQB1*0501 is 2.76 (P=0.0076).
Analysis of amino acids encoded by exon 2 of DQB1 reveal additional complexity, ...
Mots-clés Pascal : Leucémie lymphoblastique, Antigène histocompatibilité classe II, Système HLA, Système histocompatibilité majeur, Facteur risque, Epidémiologie moléculaire, Angleterre, Grande Bretagne, Royaume Uni, Europe, Enfant, Homme, Aigu, Hémopathie maligne, Lymphoprolifératif syndrome, Santé publique
Mots-clés Pascal anglais : Acute lymphocytic leukemia, Class II histocompatibility antigen, HLA-System, Major histocompatibility system, Risk factor, Molecular epidemiology, England, Great Britain, United Kingdom, Europe, Child, Human, Acute, Malignant hemopathy, Lymphoproliferative syndrome
Notice produite par :
Inist-CNRS - Institut de l'Information Scientifique et Technique
Cote : 96-0144909
Code Inist : 002B19B. Création : 199608.