TY - JOUR
T1 - HLA antigens and acute rheumatic fever
T2 - Evidence for a recessive susceptibility gene linked to HLA
AU - Hafez, M.
AU - Chakravarti, A.
AU - El-Shennawy, F.
AU - El-Morsi, Z.
AU - El-Sallab, S. H.
AU - Al-Tonbar, Y.
PY - 1985/1/1
Y1 - 1985/1/1
N2 - From 60 probands with acute rheumatic fever (ARF), 19 multiplex families segregating for ARF were ascertained. The parents and rheumatic and normal sibs of the probands in these 19 families were also studied. HLA typing using the microlymphocytotoxic assay was then performed on the 60 unrelated probands, the multiplex families, and 234 unrelated controls using 23 antigens from the HLA-A and -B loci. The controls lacked a past history of ARF and were from the same geographic locality. Calculations of relative risk demonstrate an increase of HLA-B5 antigen in the 60 patients, but the result might not be significant from the point of view of multiple comparisons. Nevertheless, affected sib pairs from the multiplex families show 93% concordance for both or one HLA haplotype. A formal linkage analysis demonstrates that a recessive etiology is most likely (lod score of 3.3) with approximately 68% of cases being due to a gene closely linked to HLA and in linkage disequilibrium with HLA-B5. The remaining 32% of cases are due to other familial factors such as polygenic inheritance or common environmental factors. The results confirm a strong genetic predisposition to ARF and its heterogeneous nature in families.
AB - From 60 probands with acute rheumatic fever (ARF), 19 multiplex families segregating for ARF were ascertained. The parents and rheumatic and normal sibs of the probands in these 19 families were also studied. HLA typing using the microlymphocytotoxic assay was then performed on the 60 unrelated probands, the multiplex families, and 234 unrelated controls using 23 antigens from the HLA-A and -B loci. The controls lacked a past history of ARF and were from the same geographic locality. Calculations of relative risk demonstrate an increase of HLA-B5 antigen in the 60 patients, but the result might not be significant from the point of view of multiple comparisons. Nevertheless, affected sib pairs from the multiplex families show 93% concordance for both or one HLA haplotype. A formal linkage analysis demonstrates that a recessive etiology is most likely (lod score of 3.3) with approximately 68% of cases being due to a gene closely linked to HLA and in linkage disequilibrium with HLA-B5. The remaining 32% of cases are due to other familial factors such as polygenic inheritance or common environmental factors. The results confirm a strong genetic predisposition to ARF and its heterogeneous nature in families.
KW - HLA antigens
KW - HLA linkage
KW - acute rheumatic fever
KW - recessive susceptibility gene
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U2 - 10.1002/gepi.1370020305
DO - 10.1002/gepi.1370020305
M3 - Article
C2 - 4054602
AN - SCOPUS:0021857487
SN - 0741-0395
VL - 2
SP - 273
EP - 282
JO - Genetic epidemiology
JF - Genetic epidemiology
IS - 3
ER -