Caputo Mariela, Cerrone Gloria E, Lopez Ariel P, Gonzalez Claudio, Mazza Carmen, Cedola Norberto, Puchulu Felix M, Targovnik Hector M, Frechtel Gustavo D
Cátedra de Genética y Biología Molecular, Facultad de Farmacia y Bioquímica, Universidad de Buenos Aires, Argentina.
Medicina (B Aires). 2005;65(3):235-40.
Autoimmune diabetes is a complex, multifactorial disease caused by the interaction of genetic and environmental factors. This autoimmune diabetes is commonly manifested in childhood and adolescence with a fast onset (type 1 diabetes, IDDM) and it can occur in adult patients with a slow onset with delayed insulin requirement, (latent autoimmune diabetes in adults, LADA ). Autoimmune diabetes has strong class II HLA association mainly with DQB gene which constitutes the first susceptibility locus. However, association with the 5'INS- VNTR and CTLA-4 genes has been established. In this study, we analysed the polimorphic allele frequencies of DQB HLA gene in 63 LADA patients, 70 IDDM and 79 control subjects. The HLA DQB1 alleles typing was detected through Olerup SSP DQ kit using sequence specific primers. We observed a positive association of *0201-*0302 and *0201-*0201 genotypes in both types of diabetic patients compared to the control group (p < 0.05). Moreover, *0201-*0302 genotype was higher in IDDM than in LADA (p < 0.05). On the other hand, the *0602 protective allele analysis showed a high prevalence in the normal group compared to the diabetic population. In Argentina, the most frequent allele of susceptibility in LADA and IDDM patients was the *0201. Summing up, the finding of an increase in the *0201 allele, both in allelic and genotypic frequencies, allows the characterisation of our population of patients, LADA and IDDM, unlike other populations, in which the most frequent allele is *0302.
自身免疫性糖尿病是一种由遗传和环境因素相互作用引起的复杂多因素疾病。这种自身免疫性糖尿病通常在儿童期和青春期发病迅速(1型糖尿病,胰岛素依赖型糖尿病,IDDM),也可发生于成年患者,起病缓慢,胰岛素需求延迟(成人隐匿性自身免疫性糖尿病,LADA)。自身免疫性糖尿病与II类HLA有很强的关联,主要与构成首个易感位点的DQB基因相关。然而,也已证实其与5'INS - VNTR和CTLA - 4基因有关联。在本研究中,我们分析了63例LADA患者、70例IDDM患者和79例对照受试者中DQB HLA基因的多态性等位基因频率。通过使用序列特异性引物的Olerup SSP DQ试剂盒检测HLA DQB1等位基因分型。与对照组相比,我们观察到两种糖尿病患者中*0201 - 0302和0201 - 0201基因型均呈正相关(p < 0.05)。此外,IDDM患者中0201 - *0302基因型高于LADA患者(p < 0.05)。另一方面,0602保护性等位基因分析显示,与糖尿病患者群体相比,正常组中的患病率较高。在阿根廷,LADA和IDDM患者中最常见的易感等位基因是0201。总之,0201等位基因在等位基因频率和基因型频率上均增加这一发现,使得我们的LADA和IDDM患者群体具有不同于其他群体的特征,在其他群体中最常见的等位基因是0302。