Cudworth A G, Wolf E
Curr Probl Clin Biochem. 1983;12:45-64.
The major genetic susceptibility to Type 1 (insulin-dependent) diabetes is determined by genes within the HLA region located on the short arm of chromosome 6. Ninety-seven percent of Type 1 diabetic patients belonging to the Barts-Windsor family study possess either DR3 or DR4 and about 50% possess both these antigens. This excess of DR3, DR4 heterozygosity can be best explained by postulating two different susceptibility genes which react in an interactive way. No increase in DR3 or DR4 homozygosity is found, nor is there an increase in recombination frequency in these families. Linkage disequilibrium between certain B and DR antigens differs in "diabetic" compared to "non-diabetic" haplotypes. In families with two or more Type 1 diabetic children, the affected siblings are with rare exception either HLA identical or haplo-identical. The results from the prospective Barts-Windsor family study indicate that complement fixing islet cell antibodies are a good marker of on-going immune destruction in the pancreatic islets. There is also a high prevalence of antibodies reacting with certain cells in the pituitary gland in newly diagnosed cases and their unaffected first degree relatives. A possible explanation is that a common virus may be acting to produce damage in several endocrine tissues. The Barts-Windsor family study was initiated in 1978 by the late Andrew Cudworth as a prospective family study to investigate the genetic, immunological and environmental factors involved in Type 1 (insulin-dependent) diabetes. About 200 families with a Type 1 diabetic child and at least one other unaffected sibling under the age of 20 years were ascertained from a defined geographical area of approximately 1500 square km, centered around Windsor, East Berkshire, UK. These families are visited every 3 to 4 months and are regularly screened for autoantibodies, in particular islet cell antibodies, and for viral antibodies and they have all been HLA-A, B, C genotyped. A large proportion have also been genotyped for HLA-DR and for the complement factors Bf, C2 and C4, which are coded by genes within the HLA-region.
1型（胰岛素依赖型）糖尿病的主要遗传易感性由位于6号染色体短臂上的HLA区域内的基因决定。参加巴茨 - 温莎家族研究的1型糖尿病患者中，97%拥有DR3或DR4，约50%同时拥有这两种抗原。DR3、DR4杂合性的这种过量现象，最好通过假定两个以相互作用方式起反应的不同易感基因来解释。未发现DR3或DR4纯合性增加，这些家族中的重组频率也未增加。与“非糖尿病”单倍型相比，某些B和DR抗原之间的连锁不平衡在“糖尿病”单倍型中有所不同。在有两个或更多1型糖尿病儿童的家庭中，受影响的兄弟姐妹几乎无一例外要么HLA完全相同，要么单倍型相同。巴茨 - 温莎家族前瞻性研究的结果表明，补体结合胰岛细胞抗体是胰腺胰岛中正在进行的免疫破坏的良好标志物。在新诊断病例及其未受影响的一级亲属中，与垂体某些细胞发生反应的抗体也有很高的患病率。一种可能的解释是，一种常见病毒可能在多个内分泌组织中造成损害。巴茨 - 温莎家族研究由已故的安德鲁·库德沃思于1978年发起，作为一项前瞻性家族研究，旨在调查1型（胰岛素依赖型）糖尿病涉及的遗传、免疫和环境因素。从英国东伯克郡温莎周围约1500平方公里的特定地理区域中，确定了约200个有一个1型糖尿病儿童且至少有一个20岁以下未受影响兄弟姐妹的家庭。这些家庭每3至4个月接受一次访问，并定期筛查自身抗体，特别是胰岛细胞抗体，以及病毒抗体，并且他们都进行了HLA - A、B、C基因分型。很大一部分家庭还进行了HLA - DR以及补体因子Bf、C2和C4的基因分型，这些基因由HLA区域内基因编码。
