Genetic susceptibility to the development of autoimmune disease

被引:92
作者
Heward, J
Gough, SCL
机构
[1] Birmingham Heartlands Hosp, Birmingham B9 5SS, W Midlands, England
[2] Univ Birmingham, Birmingham B15 2TH, W Midlands, England
基金
英国惠康基金;
关键词
autoimmunity; cytotoxic T-lymphocyte-associated-4 gene; human leucocyte antigen; inflammatory bowel disease; insulin-dependent diabetes mellitus; juvenile chronic arthritis; multiple sclerosis; psoriasis; systemic lupus erythematosus; thyroid disease;
D O I
10.1042/cs0930479
中图分类号
R-3 [医学研究方法]; R3 [基础医学];
学科分类号
1001 ;
摘要
1. Autoimmune diseases are common conditions which appear to develop in genetically susceptible individuals, with expression of disease being modified by permissive and protective environments, Familial clustering and data from twin studies provided the impetus for the search for putative loci, Both the candidate gene approach in population-based case-control studies and entire genome screening in families have helped identify susceptibility genes in a number of autoimmune diseases, 2, After the first genome screen in type 1 (insulin-dependent) diabetes mellitus it seems likely that most autoimmune diseases are polygenic with no single gene being either necessary or sufficient for disease development, Of the organ-specific autoimmune diseases, genome screens have now been completed in insulin-dependent diabetes mellitus and multiple sclerosis, Furthermore, the clustering of autoimmune diseases within the same individuals suggests that the same genes may be involved in the different diseases, This is supported by data showing that both HLA (human leucocyte antigen:, and CTLA-4 (cytotoxic T-lymphocyte-associated-4) appear to be involved in the development of insulin-dependent diabetes mellitus and Graves' disease, 3, Genome screens have also been completed in some of the non-organ-specific autoimmune diseases including rheumatoid arthritis, inflammatory bowel disease and psoriasis, Many candidate genes have also been investigated although these are predominantly in population-based case-control studies, 4, Substantial progress has been made in recent years towards the identification of susceptibility loci in autoimmune diseases, The inconsistencies seen between case-control studies may largely he due to genetic mismatching between cases and controls in small datasets, Family-based association studies are being increasingly used to confirm genetic linkages and help with fine mapping strategies, It will, however, require a combination of biology and genetics, as has been necessary with the major histocompatibility complex in insulin-dependent diabetes mellitus, to identify primary aetiological mutations.
引用
收藏
页码:479 / 491
页数:13
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