van der Auwera B J, Heimberg H, Schrevens A F, van Waeyenberge C, Flament J, Schuit F C
Department of Biochemistry, Vrije Universiteit Brussel, Belgium.
Diabetes. 1993 Jun;42(6):851-4. doi: 10.2337/diab.42.6.851.
The polymorphic variable number of tandem repeats in the 5' upstream region of the human insulin gene is a well-known non-human leukocyte antigen locus contributing to genetic susceptibility to IDDM. Controversy exists about the question as to whether INS susceptibility haplotypes are or are not preferentially inherited together with HLA-DR4 haplotypes. We investigated whether genetic interaction between INS and the HLA complex can be better defined using DQ genotypic and phenotypic markers in addition to DR serology. The 5' INS 1/1 genotype was positively associated with IDDM both in non-DR4 subjects (relative risk = 4.3; 95% confidence interval, 1.6-11.5) and DR4 subjects (relative risk = 4.2; 95% confidence interval, 1.9-9.0). Further subdivision of IDDM patients and matched control subjects according to HLA-DQA1 and HLA-DQB1 genotype or phenotype also failed to show any association between 5' INS and HLA class II genes in diabetic patients. The 5' INS and HLA class II polymorphisms therefore provide independent risk markers, which may both contribute to the genetic screening of a high-risk population among nondiabetic individuals.
人类胰岛素基因5'上游区域的串联重复序列多态性可变数目是一个众所周知的非人类白细胞抗原位点，它与IDDM的遗传易感性有关。关于INS易感单倍型是否优先与HLA - DR4单倍型一起遗传的问题存在争议。我们研究了除DR血清学外，使用DQ基因型和表型标记是否能更好地定义INS与HLA复合体之间的遗传相互作用。5' INS 1/1基因型在非DR4受试者（相对风险= 4.3；95%置信区间，1.6 - 11.5）和DR4受试者（相对风险= 4.2；95%置信区间，1.9 - 9.0）中均与IDDM呈正相关。根据HLA - DQA1和HLA - DQB1基因型或表型对IDDM患者和匹配的对照受试者进行进一步细分，也未显示糖尿病患者中5' INS与HLA II类基因之间存在任何关联。因此，5' INS和HLA II类多态性提供了独立的风险标记，它们都可能有助于在非糖尿病个体中对高危人群进行遗传筛查。
