Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes -: indication of an increased environmental pressure?
Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes -: indication of an increased environmental pressure?
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DOI：
10.1007/s00125-003-1045-4
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发表时间：
2003-03-01
期刊：
影响因子：
8.2
通讯作者：
Ilonen, J
中科院分区：
文献类型：
--
作者：
Hermann, R;Knip, M;Ilonen, J
目的/假设。在芬兰，1型糖尿病的发病率在1966年至2000年期间增加了2.5倍，这是几乎所有发达国家都出现的一个普遍趋势，只能用环境因素来解释。本研究的目的是测试环境变化对与疾病易感性相关的基因型分布的可能影响。分析HLA DRB 1-DQA 1-DQB 1基因和IDDM 2、IDDM 12位点的2个糖尿病相关多态性。比较了1939-1965年（n=367）和1990 - 2001年（n=736）诊断为儿童期发病的I型糖尿病患者的基因型频率。采用卡方统计或Fisher精确检验比较两组单倍型和基因型频率。（DR 3）-DQA 1 * 05-DQB 1 *02和（DR 4）-DQB 1 *0302危险单倍型及高危（DR 3）-DQA 1 *05-DQB 1 *021、DRB 1 *0401-DQB 1 *0302基因型频率较高，而携带保护性单倍型（DR 15）-DQB 1 *0602和（DR 1301）-DQB 1 *0603 -DQB 1 *0603 -DQB 1 * 0602的患者比例较高。与1990年后发病的患者相比，1965年前确诊的患者的保护性基因型较低。IDDM 2和IDDM 12基因型频率无时间变异。我们的数据表明，随着时间的推移，由于环境压力的增加，遗传易感性发展为I型糖尿病的需求已经下降，这导致疾病进展率更高，特别是在具有保护性HLA基因型的受试者中。
Aims/hypothesis. The incidence of Type 1 diabetes has increased 2.5 times during the time period from 1966 to 2000 in Finland - a general trend seen in almost all developed countries that can only be explained by environmental factors. The aim of this study was to test the possible effect of a changing environment on distribution of genotypes associated with disease susceptibility.Methods. HLA DRB1-DQA1-DQB1 genes and two diabetes-associated polymorphisms at IDDM2 and IDDM12 were analyzed. The frequencies of genotypes were compared between cases diagnosed with childhood-onset Type I diabetes during the period of 1939-1965 (n=367) and those diagnosed between 1990 and 2001 (n=736). Chi-square statistics or the Fisher's Exact test were used for the comparison of frequencies of analyzed haplotypes and genotypes in the two groups.Results. The frequencies of (DR3)-DQA1*05DQB1*02 and (DR4)-DQB1*0302 risk haplotypes and the high risk (DR3)-DQA1*05-DQB1*021 DRB1*0401-DQB1*0302 genotype were higher while proportion of patients carrying protective haplotypes (DR15)-DQB1*0602 and (DR1301)-DQB1*0603 - or protective genotypes was lower in patients diagnosed before 1965 as compared to those who developed disease after 1990. No temporal variation was found in the frequencies of genotypes at IDDM2 land IDDM12.Conclusion/interpretation. Our data suggest that the need for genetic susceptibility to develop Type I diabetes has decreased over time due to an increasing environmental pressure and this results in a higher disease progression rate especially in subjects with protective HLA genotypes.