Pirie F J, Pegoraro R, Motala A A, Rauff S, Rom L, Govender T, Esterhuizen T M
Department of Medicine, Nelson R Mandela School of Medicine, University of KwaZulu-Natal, Durban, South Africa.
Tissue Antigens. 2005 Aug;66(2):125-30. doi: 10.1111/j.1399-0039.2005.00454.x.
Type 1 diabetes is the consequence of exposure of genetically susceptible individuals to specific environmental precipitants. The innate immune system provides the initial response to exogenous antigen and links with the adaptive immune system. The aim of this study was to assess the role of polymorphisms occurring in the cytoplasmic region of toll-like receptor (TLR) 3 gene and immediate 5' sequence, in subjects of Zulu descent with type 1 diabetes in KwaZulu-Natal, South Africa. Seventy-nine subjects with type 1 diabetes and 74 healthy normal glucose tolerant gender-matched control subjects were studied. Parts of exon 4 and exon 3/intron 3 of the TLR3 gene were studied by polymerase chain reaction, direct sequencing and restriction enzyme digestion with Bts 1. Of the nine polymorphisms studied, a significant association with type 1 diabetes was found for the major allele in the 2593 C/T polymorphism and for the minor alleles in the 2642 C/A and 2690 A/G polymorphisms, which were found to be in complete linkage disequilibrium. Correction of the P-values for the number of alleles studied, however, rendered the results no longer significant. These results suggest that polymorphisms in the TLR3 gene, which is part of the innate immune system, may be associated with type 1 diabetes in this population.
1型糖尿病是遗传易感个体暴露于特定环境诱发因素的结果。先天免疫系统对外源抗原产生初始反应，并与适应性免疫系统相联系。本研究的目的是评估在南非夸祖鲁-纳塔尔省祖鲁族血统的1型糖尿病患者中，Toll样受体（TLR）3基因胞质区及紧邻的5'序列中发生的多态性的作用。研究了79例1型糖尿病患者和74例健康的糖耐量正常的性别匹配对照者。通过聚合酶链反应、直接测序以及用Bts 1进行限制性内切酶消化，对TLR3基因的外显子4部分以及外显子3/内含子3进行了研究。在所研究的9种多态性中，发现2593 C/T多态性的主要等位基因以及2642 C/A和2690 A/G多态性的次要等位基因与1型糖尿病存在显著关联，这几种多态性处于完全连锁不平衡状态。然而，对所研究等位基因数量进行P值校正后，结果不再具有显著性。这些结果表明，作为先天免疫系统一部分的TLR3基因中的多态性可能与该人群的1型糖尿病有关。
