Pérez-Bravo F, Santos J L, Carrasco E, Calvillán M, Albala C, Puig-Domingo M, Piquer S, De Leiva A
Molecular Biology Laboratory, INTA, University of Chile, Santiago, Spain.
Autoimmunity. 2001;33(4):285-91.
The purpose of this study was to assess whether the transmission of DQB10201 and DQB10302 alleles from heterozygous parents to Chilean type 1 diabetic patients depends on the presence of antibodies such as glutamic acid decarboxilase (GAD65) or Islet Cell (ICA) autoantibodies in the affected case.
A study of incident type 1 diabetic cases and parents was carried out in Santiago, Chile during 1997-98. The use of the case-parental design eliminates the possibility that case-controls differences are due to selection of controls whose genetic backgrounds differ systematically from those of cases. HLA-DQB1 polymorphisms were determined in cases and parents from n = 83 families using polymerase chain reaction and oligonucleotide dot-blot analysis. Detection of GAD65 antibodies was performed using a simple radio-binding asssay. Conventional ICA were detected by indirect immunofluorescence.
Transmission disequilibrium test indicate a strong association between DQB10201 and DQB10302 and type I diabetes. When comparing the two subsets of families defined by having an affected child tested negative or positive for GAD65 antibodies (39 and 44 case-parent trios respectively) the probability of transmission of DQB10201 significantly differed between such strata (p-value=0.025). The pattern of transmission of DQB1201 allele was also significantly different in the two subsets of families defined by ICA-or ICA+ cases (23 and 60 trios respectively) (p-value = 0.028). No differences were found in the transmission of DQB1*0302 allele in the different strata defined by the autoimmunity status of the proband.
Our results reveal that DQB1*0201 allele may display distinct associations with type I diabetes depending on the autoimmunity to ICA and GAD65 autoantibodies.
本研究旨在评估杂合子父母的DQB10201和DQB10302等位基因向智利1型糖尿病患者的传递是否取决于患病个体中谷氨酸脱羧酶（GAD65）或胰岛细胞（ICA）自身抗体等抗体的存在情况。
1997年至1998年期间在智利圣地亚哥对新发病的1型糖尿病病例及其父母进行了一项研究。病例-父母设计的使用消除了病例对照差异是由于选择了遗传背景与病例有系统差异的对照的可能性。使用聚合酶链反应和寡核苷酸斑点杂交分析确定了来自n = 83个家庭的病例及其父母的HLA-DQB1多态性。使用简单的放射结合试验检测GAD65抗体。通过间接免疫荧光检测传统的ICA。
传递不平衡检验表明DQB10201和DQB10302与1型糖尿病之间存在强关联。当比较由患病儿童GAD65抗体检测呈阴性或阳性定义的两个家庭子集时（分别为39个和44个病例-父母三联体），DQB10201在这些阶层之间的传递概率有显著差异（p值 = 0.025）。在由ICA阴性或ICA阳性病例定义的两个家庭子集（分别为23个和60个三联体）中，DQB1201等位基因的传递模式也有显著差异（p值 = 0.028）。在先证者自身免疫状态定义的不同阶层中，DQB1*0302等位基因的传递没有发现差异。
我们的结果表明，根据对ICA和GAD65自身抗体的自身免疫情况，DQB1*0201等位基因可能与1型糖尿病表现出不同的关联。
