HISTOCOMPATIBILITY SYSTEM IN JUVENILE, INSULIN-DEPENDENT DIABETIC MULTIPLEX KINDREDS
HISTOCOMPATIBILITY SYSTEM IN JUVENILE, INSULIN-DEPENDENT DIABETIC MULTIPLEX KINDREDS
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DOI：
10.1172/jci108879
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发表时间：
1977-01-01
影响因子：
15.9
通讯作者：
YUNIS, EJ
中科院分区：
文献类型：
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作者：
BARBOSA, J;KING, R;YUNIS, EJ
组织相容性（HLA）基因型确定了24个家庭与2个或更多的青少年，胰岛素依赖，酮症倾向的糖尿病兄弟姐妹。家庭选择的这个标准被用来获得一个同质形式的糖尿病的同胞，因为糖尿病似乎是一种遗传异质性疾病。58糖尿病和53非糖尿病同胞和40父母进行了研究。在糖尿病患者对中，55%的患者两种HLA单倍型一致（预期为25%），40%的患者一种单倍型一致（预期为50%），5%的患者两种单倍型不一致（预期为25%）。这些值与预期值有显著差异（P < 0.001）。在这些家庭中的非糖尿病同胞之间的单倍型遗传没有显着不同的预期孟德尔分离。当比较20对HLA相合（共有2个单倍型）和15对单倍相合（共有1个单倍型）的糖尿病同胞的发病年龄对内差异时，HLA相合同胞的发病年龄（差异3.9岁）比单倍相合同胞（差异7.3岁）的发病年龄更一致（P < 0.05）。对月份中季节性发病率差异的相同类型分析显示，HLA相同的同胞更一致（1.8个月）。差异）比单倍相合同胞（3.2 mo.差异有显著性（P < 0.025）。HLA相合的糖尿病同胞在冬季更容易患糖尿病（78%），而单倍体相合的糖尿病同胞（21%）。没有特定的HLA单倍型或抗原似乎与任何特定的临床特征。这些数据与青少年胰岛素依赖型糖尿病的遗传异质性理论是一致的。可能有一个或多个糖尿病反应基因在HLA区域发挥重要作用的发病机制中的青少年，胰岛素依赖型糖尿病在这里研究的家庭。有可能是其他基因，不相关的HLA复合体，可能在某些情况下，青少年，胰岛素依赖型糖尿病的病因中发挥作用，导致HLA和某些形式的糖尿病之间缺乏关联。
Histocompatibility (HLA) genotypes were determined for 24 families with 2 or more juvenile, insulin-dependent, ketosis-prone diabetic siblings. This criterion for family selection was used to obtain a homogeneous form of diabetes within a sibship, because diabetes appears to be a genetically heterogeneous disease. Fifty-eight diabetic and 53 nondiabetic sibs and 40 parents were studied. Of the diabetic pairs 55% were concordant for both HLA haplotypes (expected 25%), 40% were concordant for 1 haplotype (expected 50%), and 5% were discordant for both haplotypes (expected 25%). These values are significantly different from the expected values (P < 0.001). The inheritance of haplotypes among the nondiabetic sibs in these families was not significantly different from the expected mendelian segregation. When comparing 20 pairs of HLA identical (sharing 2 haplotypes) with 15 pairs of haploidentical (sharing 1 haplotype) diabetic sibs for the intrapair difference in age of onset of disease, the HLA identical sibs were significantly more concordant for age of onset (3.9 yr difference) than the haploidentical (7.3 yr difference) (P < 0.05). The same type of analysis for the difference in seasonal incidence in months revealed that the HLA identical sibs were more concordant (1.8 mo. difference) than the haploidentical sibs (3.2 mo. difference) (P < 0.025). The HLA identical diabetic sibs were more likely to develop diabetes in the winter months (78%) than the haploidentical diabetic sibs (21%). No particular HLA haplotype or antigen seemed to be associated with any particular clinical feature. These data are compatible with the theory of genetic heterogeneity of juvenile, insulin-dependent diabetes. There may be one or more diabetes response genes in the HLA region playing an important role in the pathogenesis of juvenile, insulin-dependent diabetes in the families studied here. It is possible that other genes, not associated with the HLA complex, may play an etiologic role in some cases of juvenile, insulin-dependent diabetes, resulting in lack of association between HLA and some forms of diabetes.