Ilonen J, Reijonen H, Green A, Reunanen A, Knip M, Simell O, Akerblom H K
Department of Virology, University of Turku, Finland.
Eur J Immunogenet. 2000 Aug;27(4):225-30. doi: 10.1046/j.1365-2370.2000.00223.x.
Geographical variations in the HLA-DQ genotypes associated with risk for type 1 diabetes were evaluated in Finland. Samples of 280 diabetic children diagnosed in Turku (south-west of the country) and 405 in Oulu (north of the country) were studied as well as a series of 14 096 and 10 016 newborns collected from the same hospitals. There were no major differences in the risk or protection conferred by various HLA-DQB1 genotypes between south-western and northern parts of the country when genotypes of children with type 1 diabetes from these two centres were compared with those of newborns, representing the background populations. However, the distribution of various genotypes was different, both in diabetic children and in newborns, when compared between the two regions (P < 0.0001, chi2 test). These differences reflected the allele frequencies in newborn cohorts in which HLA-DQB102 and DQB10301 were found more often in Turku and DQB1*0302 more often in Oulu (P < 0.0001 for all differences). Similar types of differences were detected when children who were diagnosed as having diabetes during the national 'Childhood Diabetes in Finland' (DiMe) study between the years 1986-1989 were compared according to their residence. The observed differences in genotype and allele frequencies demonstrate the heterogeneity for HLA alleles even in a population that is generally regarded as highly homogeneous. These differences also affect the sensitivity and efficiency of the screening programme used for identifying infants with genetic susceptibility to IDDM in the ongoing Finnish Diabetes Prediction and Prevention Study.
在芬兰,对与1型糖尿病风险相关的HLA - DQ基因型的地理差异进行了评估。研究了在图尔库(该国西南部)诊断出的280名糖尿病儿童和在奥卢(该国北部)诊断出的405名糖尿病儿童的样本,以及从同一医院收集的一系列14096名和10016名新生儿的样本。将这两个中心的1型糖尿病儿童的基因型与代表背景人群的新生儿的基因型进行比较时,该国西南部和北部由各种HLA - DQB1基因型赋予的风险或保护作用没有重大差异。然而,当比较这两个地区的糖尿病儿童和新生儿时,各种基因型的分布是不同的(P < 0.0001,卡方检验)。这些差异反映了新生儿队列中的等位基因频率,其中在图尔库更常发现HLA - DQB102和DQB10301,在奥卢更常发现DQB1*0302(所有差异的P < 0.0001)。当根据居住地对1986 - 1989年全国“芬兰儿童糖尿病”(DiMe)研究期间被诊断患有糖尿病的儿童进行比较时,也检测到了类似类型的差异。观察到的基因型和等位基因频率差异表明,即使在通常被认为高度同质的人群中,HLA等位基因也存在异质性。这些差异也影响了正在进行的芬兰糖尿病预测和预防研究中用于识别对IDDM有遗传易感性的婴儿的筛查计划的敏感性和效率。