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SUMO4 M55V基因多态性与拉脱维亚患者自身免疫性糖尿病的关联

Association of SUMO4 M55V polymorphism with autoimmune diabetes in Latvian patients.

作者信息

Sedimbi Saikiran K, Shastry Arun, Park Yongsoo, Rumba Ingrida, Sanjeevi Carani B

机构信息

Karolinska Institute, Department of Molecular Medicine, Karolinska Hospital Campus, CMM L5:01, S-17176 Stockholm, Sweden.

出版信息

Ann N Y Acad Sci. 2006 Oct;1079:273-7. doi: 10.1196/annals.1375.041.

Abstract

Small ubiquitin-related modifier (SUMO4), located in IDDM5, has been identified as a potential susceptibility gene for type 1 diabetes mellitus (T1DM). The novel polymorphism M55V, causing an amino acid change in the evolutionarily conserved met55 residue has been shown to activate the nuclear factor kappaB (NF-kappaB), hence the suspected role of SUMO4 in the pathogenicity of T1DM. The M55V polymorphism has been shown to be associated with susceptibility to T1DM in Asians, but not in Caucasians. Latent autoimmune diabetes in adults (LADA) is a slowly progressive form of T1DM and SUMO4 M55V has not been studied in LADA to date. The current study aims to test whether Latvians are similar to Caucasians in susceptibility to autoimmune diabetes (T1DM and LADA), with respect to SUMO4 M55V. We studied, age- and sex-matched, Latvian T1DM patients (n = 100) and healthy controls (n = 90) and LADA patients (n = 45) and healthy controls (n = 95). SUMO4 M55V polymorphism was analyzed using polymerase chain reaction (PCR)-restriction fragment length polymorphism (RFLP). The allelic frequencies of the A and G alleles were compared with HLA DR3-DR4-positive and HLA DR3-DR4-negative patients to identify any potential relation between HLA DR3-DR4 and SUMO4 M55V. We found no significant association between SUMO4 M55V and T1DM susceptibility in Latvians, the results being in concurrence with the previous studies in Caucasians of British and Canadian origin. Comparison of the A and G alleles with HLA DR3-DR4 did not result in any significant P values. No significant association was found between SUMO4 M55V and LADA. SUMO4 M55V is not associated with susceptibility to T1DM and LADA in Latvians, and Latvians exhibit similarity to other Caucasians with respect to association of SUMO4 M55V with autoimmune diabetes.

摘要

位于IDDM5的小泛素相关修饰因子(SUMO4)已被确定为1型糖尿病(T1DM)的一个潜在易感基因。新型多态性M55V导致进化保守的甲硫氨酸55残基发生氨基酸变化,已被证明可激活核因子κB(NF-κB),因此怀疑SUMO4在T1DM的发病机制中起作用。M55V多态性已被证明与亚洲人患T1DM的易感性相关,但与高加索人无关。成人隐匿性自身免疫性糖尿病(LADA)是T1DM的一种缓慢进展形式,迄今为止尚未对LADA中的SUMO4 M55V进行研究。当前研究旨在测试就SUMO4 M55V而言,拉脱维亚人在自身免疫性糖尿病(T1DM和LADA)易感性方面是否与高加索人相似。我们研究了年龄和性别匹配的拉脱维亚T1DM患者(n = 100)和健康对照者(n = 90)以及LADA患者(n = 45)和健康对照者(n = 95)。使用聚合酶链反应(PCR)-限制性片段长度多态性(RFLP)分析SUMO4 M55V多态性。将A和G等位基因的频率与HLA DR3-DR4阳性和HLA DR3-DR4阴性患者进行比较,以确定HLA DR3-DR4与SUMO4 M55V之间的任何潜在关系。我们发现SUMO4 M55V与拉脱维亚人患T1DM的易感性之间无显著关联,结果与先前对英国和加拿大血统高加索人的研究一致。将A和G等位基因与HLA DR3-DR4进行比较未得出任何显著的P值。未发现SUMO4 M55V与LADA之间存在显著关联。SUMO4 M55V与拉脱维亚人患T1DM和LADA的易感性无关,并且在SUMO4 M55V与自身免疫性糖尿病的关联方面,拉脱维亚人与其他高加索人表现出相似性。

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