1型(胰岛素依赖型)糖尿病的遗传学。

A G Cudworth, E Wolf
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引用次数: 0

摘要

1型(胰岛素依赖性)糖尿病的主要遗传易感性是由位于6号染色体短臂上的HLA区域内的基因决定的。属于bart - windsor家族研究的97%的1型糖尿病患者拥有DR3或DR4,约50%的患者同时拥有这两种抗原。过量的DR3、DR4杂合性可以通过假设两种不同的易感基因以相互作用的方式反应来最好地解释。在这些家族中,没有发现DR3或DR4纯合性增加,也没有发现重组频率增加。在“糖尿病”和“非糖尿病”单倍型中,某些B和DR抗原之间的连锁不平衡是不同的。在有两个或两个以上1型糖尿病儿童的家庭中,受影响的兄弟姐妹除了罕见的例外是HLA相同或单倍相同。前瞻性的bart - windsor家族研究结果表明,补体固定胰岛细胞抗体是胰岛正在进行的免疫破坏的良好标记。在新诊断的病例及其未受影响的一级亲属中,抗体与脑垂体中某些细胞的反应也很普遍。一种可能的解释是,一种常见的病毒可能会对几种内分泌组织造成损害。Barts-Windsor家族研究是由已故的Andrew Cudworth于1978年发起的,作为一项前瞻性家庭研究,旨在调查与1型(胰岛素依赖型)糖尿病相关的遗传、免疫和环境因素。在英国东伯克郡温莎中心约1500平方公里的限定地理区域内,确定了大约200个有1型糖尿病儿童和至少一个未受影响的20岁以下兄弟姐妹的家庭。每3到4个月对这些家庭进行一次访问,定期筛查自身抗体,特别是胰岛细胞抗体和病毒抗体,这些抗体都是HLA-A, B, C基因型。也有很大比例的人对HLA-DR和补体因子Bf、C2和C4进行了基因分型,这些补体因子由hla区域内的基因编码。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
The genetics of Type 1 (insulin-dependent) diabetes.

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.

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