Geographical variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of β-cell autoimmunity in a high-incidence country
Geographical variation in risk HLA-DQB1 genotypes for type 1 diabetes and signs of β-cell autoimmunity in a high-incidence country
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DOI：
10.2337/diacare.27.3.676
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发表时间：
2004-03-01
期刊：
影响因子：
16.2
通讯作者：
Knip, M
中科院分区：
文献类型：
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作者：
Kukko, M;Virtanen, SM;Knip, M
目的-评估HLA-DQB 1风险基因型的频率和β细胞自身免疫性的迹象出现之间的三个地理区域在Finland.Research设计和方法的可能差异-系列。包括来自糖尿病预测和预防（DIPP）研究的4，642名HLA-DQB 1定义的1型糖尿病遗传风险增加的儿童：1，793名（38.6%）出生于图尔库，1，646名（35.5%）出生于欧卢，1，203名（25.9%）出生于坦佩雷。经常检查这些儿童是否出现β细胞自身免疫迹象，并使用胰岛细胞抗体（伊卡）进行初步筛查。如果孩子患上伊卡，所有样本还分析了胰岛素自身抗体（IAA）、GADA 65抗体（GADA）和IA-2分子抗体（IA-2A）。高危基因型在欧卢地区（20.4%）的频率低于图尔库（28.4%; P < 0.001）或坦佩雷地区（27.2%; P < 0.001）。相对于中度风险基因型，该基因型与伊卡血清转换频率增加相关（风险比1.89，95%CI 1.36-2.62）。伊卡阳性血清转化在坦佩雷的发生率低于图尔库（0.47，0.28。欧卢的血清转化率与图尔库的血清转化率无差异（0.72，0：51-1.03）。在调整了风险基因型、性别和出生时间（1998年1月之前与之后）后，坦佩雷-图尔库差异仍然存在。至少一个额外的自身抗体的血清转换也较不常见的坦佩雷比在图尔库（0.39，0.16-0.82）。结论-这些数据表明，在芬兰，1型糖尿病的发病率最高的国家在世界上，高风险的HLA-DQB 1基因型的频率和自身抗体阳性的血清转换的风险显示地理变异。血清转换率的差异不能用HLA-DQB 1定义的疾病易感性的差异来解释，这意味着糖尿病相关自身免疫的环境触发因素的影响可能在研究的三个地区之间存在差异。
OBJECTIVE - To assess possible differences in the frequency of HLA-DQB1 risk genotypes and the emergence of signs of beta-cell autoimmunity among three geographical regions in Finland.RESEARCH DESIGN AND METHODS- The series. comprised 4,642 children with increased HLA-DQB1-defined genetic risk of type 1 diabetes from the Diabetes Prediction and Prevention (DIPP) study: 1,793 (38.6%) born in Turku, 1,646 (35.5%) in Oulu, and 1,203 (25.9%) in Tampere. These children were examined frequently for the emergence of signs of beta-cell autoimmunity, for the primary screening of which islet cell antibodies (ICA) were used. If the child developed ICA, all samples were also analyzed for insulin autoantibodies (IAA), GAD65 antibodies (GADA), and antibodies to the IA-2 molecule (IA-2A).RESULTS- The high- and moderate-risk genotypes were unevenly distributed among the three areas (P < 0.001); the high-risk genotype was less frequent in the Oulu region (20.4%) than in the Turku (28.4%; P < 0.001) or Tampere regions (27.2%; P < 0.001). This genotype was associated with an increased frequency of ICA seroconversion relative to the moderate risk genotypes (hazard ratio 1.89, 95% CI 1.36-2.62). Seroconversions to ICA positivity occurred less commonly in Tampere than in Turku (0.47, 0.28.-0.75), whereas the seroconversion rate in Oulu did not differ from that in Turku (0.72, 0:51-1.03). The Tampere-Turku difference persisted after adjustment for risk genotypes, sex, and time of birth (before January 1998 versus later). Seroconversion for at least one additional autoantibody was also less frequent in Tampere than in Turku (0.39, 0.16-0.82).CONCLUSIONS - These data show that in Finland, the country with the highest incidence of type 1 diabetes in the world, both the frequency of the high-risk HLA-DQB1 genotype and the risk of seroconversion to autoantibody positivity show geographical variation. The difference in seroconversion rate could not be explained by the difference in HLA-DQB1-defined disease susceptibility, implying that the impact of environmental triggers of diabetes-associated autoimmunity may differ between the three regions studied.