Trinucleotide repeats of programmed cell death-1 gene are associated with susceptibility to type 1 diabetes mellitus.
Trinucleotide repeats of programmed cell death-1 gene are associated with susceptibility to type 1 diabetes mellitus.
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DOI：
10.1016/j.metabol.2007.01.021
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发表时间：
2007-07
期刊：
影响因子：
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通讯作者：
Y. Hiromine;H. Ikegami;T. Fujisawa;K. Nojima;Y. Kawabata;S. Noso;Katsuaki Asano;Aya Fukai;T. Ogihara
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文献类型：
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作者：
Y. Hiromine;H. Ikegami;T. Fujisawa;K. Nojima;Y. Kawabata;S. Noso;Katsuaki Asano;Aya Fukai;T. Ogihara
多个基因参与赋予自身免疫性1型糖尿病的易感性。免疫受体程序性细胞死亡-1（PDCD-1）是一种调节外周耐受的抑制性共刺激分子，据报道在1型糖尿病的发展中起重要作用，使人PDCD-1基因PDCD-1成为疾病易感性的候选者。本研究的目的是阐明PDCD 1对人类1型糖尿病遗传易感性的贡献。为了筛选序列变异，我们对日本受试者PDCD 1的所有5个外显子和外显子-内含子连接进行了测序，其中16例患有1型糖尿病，16例没有这种疾病。通过聚合酶链反应限制性片段长度多态性方法或基于荧光的方法，在较大的样本（n = 275）中确定了一些序列变异的基因型，有和没有1型糖尿病。采用列联表分析和Pearson χ 2检验比较1型糖尿病患者和健康对照者的多态性分布。在本研究中，我们发现了16个序列变异，包括3′非翻译区的TGC重复变异。我们发现这种变异与1型糖尿病的发生有关。这些数据表明PDCD 1及其基因产物对1型糖尿病的发展有贡献。
Multiple genes are involved in conferring susceptibility to autoimmune type 1 diabetes mellitus. The immunoreceptor programmed cell death-1 (PDCD-1), an inhibitory costimulatory molecule regulating peripheral tolerance, is reported to play an important role in the development of type 1 diabetes mellitus, making the human PDCD-1 gene, PDCD1, a candidate for disease susceptibility. The aim of this study was to clarify the contribution of PDCD1 to genetic susceptibility to type 1 diabetes mellitus in humans. To screen for sequence variants, we sequenced all 5 exons and exon-intron junctions of PDCD1 in Japanese subjects, 16 with type 1 diabetes mellitus and 16 without the disease. Some of the sequence variations identified were genotyped in larger samples (n = 275) with and without type 1 diabetes mellitus by polymerase chain reaction restriction fragment length polymorphism method or a fluorescence-based method. The distributions of polymorphisms were compared between patients with type 1 diabetes mellitus and healthy controls by contingency table analysis and Pearson χ2test. In this study, we found 16 sequence variants, including a TGC repeating variant in the 3′ untranslated region. We found this variant to be associated with the development of type 1 diabetes mellitus. These data suggest the contribution of PDCD1 and its gene product to the development of type 1 diabetes mellitus.