Gupta M, Ludvigsson J, Sanjeevi C B
Molecular Immunogenetics, CMM; L8:00, Karolinska Hospital, S-17176, Stockholm, Sweden.
Ann N Y Acad Sci. 2004 Dec;1037:138-44. doi: 10.1196/annals.1337.023.
Type 1 diabetes mellitus (T1DM) is an autoimmune disease known to occur in genetically susceptible individuals after exposure to certain unknown environmental factors. HLA-DR3-DQ2 or DR4-DQ8 are established genetic markers for the disease. MHC class I chain-related gene-A (MICA) gene polymorphism has been proposed to be associated with T1DM. To identify the environmental factors and for implementing intervention trials to prevent T1DM, it is important to screen subjects at genetically increased risk for developing T1DM. The All Babies in Southeast Sweden (ABIS) study aims to assess the risk of future progression to T1DM in the general child population. In the present report, we studied the frequency of MICA alleles among newborn babies carrying high-risk HLA DQ2 or DQ8. Of 2821 newborns, we found 563 subjects positive for DQ2, 583 subjects positive for DQ8, 133 subjects positive for DQ2-DQ8 (heterozygous), and 1013 subjects positive for either DQ2 or DQ8. Of these 1013 babies, we typed 499 babies for MICA. Frequency of MICA5 was 38% among DQ8+, 35% among for DQ2-DQ8 (heterozygous) positives, and 22.5% among DQ2+ babies. Frequency of MICA5.1 was 81% among DQ+, 62% among DQ8+, and 71% among DQ2-DQ8 (heterozygous) positives. Frequency of MICA6 was between 20% and 22% among the three groups. Frequency of MICA5/5.1 was 19% among DQ2-DQ8 (heterozygous) positives and between 12% and 13% among those positive for DQ2, DQ8, DQ2, or DQ8. The results from genetic typing in this study would be useful, in conjunction with results from autoantibody analysis that are prospectively being followed-up in all the babies, to develop an approach for identifying children at risk for developing T1DM. Inclusion of MICA typing in addition to HLA could be useful for screening of genetic markers associated with T1DM.
1型糖尿病（T1DM）是一种自身免疫性疾病，已知在遗传易感个体暴露于某些未知环境因素后发生。HLA - DR3 - DQ2或DR4 - DQ8是该疾病已确定的遗传标记。有人提出MHC I类链相关基因A（MICA）基因多态性与T1DM相关。为了确定环境因素并开展预防T1DM的干预试验，筛查有遗传易感性发展为T1DM的个体非常重要。瑞典东南部所有婴儿（ABIS）研究旨在评估普通儿童群体未来发展为T1DM的风险。在本报告中，我们研究了携带高危HLA DQ2或DQ8的新生儿中MICA等位基因的频率。在2821名新生儿中，我们发现563名DQ2阳性受试者，583名DQ8阳性受试者，133名DQ2 - DQ8（杂合子）阳性受试者，以及1013名DQ2或DQ8阳性受试者。在这1013名婴儿中，我们对499名婴儿进行了MICA分型。MICA5在DQ8 +中的频率为38%，在DQ2 - DQ8（杂合子）阳性中的频率为35%，在DQ2 +婴儿中的频率为22.5%。MICA5.1在DQ +中的频率为81%，在DQ8 +中的频率为62%，在DQ2 - DQ8（杂合子）阳性中的频率为71%。MICA6在三组中的频率在20%至22%之间。MICA5 / 5.1在DQ2 - DQ8（杂合子）阳性中的频率为19%，在DQ2、DQ8、DQ2或DQ8阳性中的频率在12%至13%之间。本研究的基因分型结果，结合所有婴儿正在前瞻性随访的自身抗体分析结果，将有助于制定一种识别有发展为T1DM风险儿童的方法。除HLA外纳入MICA分型可能有助于筛查与T1DM相关的遗传标记。
