Polymorphism in the Human Complement C4 Genes and Genetic Susceptibility to Autoimmune Hepatitis
作者:
DohertyDerek G.,
UnderhillJames A.,
DonaldsonPeter T.,
ManabeKoji,
MieliGiorgina,
EddlestonAdrian L.W.F.,
VerganiDiego,
DemaineAndrew G.,
WilliamsRoger,
期刊:
Autoimmunity
(Taylor Available online 1994)
卷期:
Volume 18,
issue 4
页码: 243-249
ISSN:0891-6934
年代: 1994
DOI:10.3109/08916939409009525
出版商: Taylor&Francis
关键词: autoimmune hepatitis;major histocompatibility complex;complement;DNA polymorphism
数据来源: Taylor
摘要:
Susceptibility to autoimmune hepatitis is associated with the HLA-DR3 and DR4 haplotypes, but which genes are directly involved in the pathogenesis, has not been established. Low levels of complement component C4 and elevated frequencies of C4 null allotypes have been described in patients, suggesting that the C4 genes, which are closely linked with the HLA loci, may play a role. We therefore examined restriction fragment length polymorphisms in the C4 and 21-hydroxylase genes, and determined HLA-A and B phenotypes, and HLA-DR, DQ and DP genotypes in a large series of Caucasoid patients with autoimmune hepatitis and matched controls. A DNA deletion of the C4A gene and the 21-hydroxylase A pseudogene was found to be present in 50% of patients compared to 23% of controls(Pc<0.005, relative risk = 3.3). This increase, however, appears to be due to linkage disequilibrium with HLA-DR52a which was most strongly associated with the disease. Complete C4A deficiency, determined by homozygosity for the deletion increased the risk to 18.1 (16% versus 1%,Pc<0.005), suggesting an additional role for C4 in disease susceptibility. C4 deletions were associated with an increased mortality and tendency to relapse whilst on treatment but did not correlate with age of onset of disease. Our data suggest that MHC-encoded susceptibility to autoimmune hepatitis is polygenic, involving the HLA-DR genes plus other loci, and C4 deficiency may be a marker of disease susceptibility and/or severity.
点击下载:
PDF (687KB)
返 回