Genetic Risk Markers Related to Diabetes-Associated Autoantibodies in Young Patients with Type 1 Diabetes in Berlin, Germany
Genetic Risk Markers Related to Diabetes-Associated Autoantibodies in Young Patients with Type 1 Diabetes in Berlin, Germany
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DOI：
10.1055/s-0029-1246213
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发表时间：
2010-04-01
影响因子：
1.8
通讯作者：
Ilonen, J.
中科院分区：
文献类型：
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作者：
Kordonouri, O.;Hartmann, R.;Ilonen, J.
为确定德国一个中心诊断的儿童1型糖尿病（T1 D）遗传风险标志物的患病率，并评估其与糖尿病相关自身抗体的关系，对243例儿童患者的血液样本进行高危HLA单倍型DR 3-DQ 2基因分型（DQA 1 *05-DQB 1 *02）和DR 4-DQ 8（DRB 1 *0401/2/4/5-DQB 1 *0302）和PTPN 22 C1858 T多态性。患者（51.4%男性）在中位年龄8.6岁时被诊断为T1 D。在诊断时分析T1 D相关自身抗体GADA、IAA和IA-2A。166例患者（68.6%）携带DR 3-DQ 2，114例（47.1%）携带DR 4-DQ 8单倍型，而41例（16.9%）患者两者均为阴性。PTPN 22 CC基因型177例（72.8%），CT基因型58例（23.9%），TT基因型8例（3.3%）。IA-2A、GADA和IAA的T1 D相关自身免疫的患病率分别为77.0%、71.6%和43.6%。有和无1858 T等位基因的患者在自身抗体的频率、水平或数量方面没有差异，但前者在诊断时比后者年轻（p=0.002），IA-2A与HLA DR 4-DQ 8正相关（p=0.004），与HLA DR 3-DQ 2负相关（p=0.002）。GADA阳性患者的年龄大于GADA阴性患者（p=0.004）。在以性别和年龄为混杂变量的多因素logistic回归分析中，DR 4-DQ 8（OR 2.56，95%CI 1.35-4.86）和DR 3-DQ 2（或0.36，95%CI 0.19-0.68）是IA的唯一独立预测因子。发现患有T1 D的柏林儿童中遗传风险标记的流行率与其他高加索T1 D人群相当。诊断时IA-2A的存在与HLA风险单倍型密切相关，但与PTPN 22多态性无关。
To determine the prevalence of genetic risk markers of type 1 diabetes (T1D) in children diagnosed at a single centre in Germany and to assess their relation to diabetes-associated autoantibodies.Blood samples from 243 paediatric patients were genotyped for the high-risk HLA haplotypes DR3-DQ2 (DQA1*05-DQB1*02) and DR4-DQ8 (DRB1*0401/2/4/5-DQB1*0302) and PTPN22 C1858T polymorphism. The patients (51.4% male) were diagnosed with T1D at a median age of 8.6y. The T1D-related autoantibodies GADA, IAA and IA-2A were analysed at diagnosis.166 patients (68.6%) carried the DR3-DQ2, 114 (47.1%) the DR4-DQ8 haplotype, while 41 (16.9%) patients were negative for both. The PTPN22 CC genotype was detected in 177 (72.8%), CT in 58 (23.9%) and TT in eight (3.3%) patients, respectively. The prevalence of T1D-related autoimmunity was 77.0% for IA-2A, 71.6% for GADA and 43.6% for IAA. There were no differences between patients with and without the 1858 T allele in terms of the frequency, levels or number of autoantibodies, but the former were younger at diagnosis than the latter (p=0.002), IA-2A were positively related to HLA DR4-DQ8 (p=0.004) and inversely associated with HLA DR3-DQ2 (p=0.002). GADA-positive patients were older than those without GADA (p=0.004). In multivariate logistic regression analysis including gender and age as confounding variables, DR4-DQ8 (OR 2.56, 95%CI 1.35-4.86) and DR3-DQ2 (OR 0.36, 95%CI 0.19-0.68) were the only independent predictors of IA-2A positivity.The prevalence of genetic risk markers in Berlin children with T1D is found to be comparable to other Caucasian T1D populations. The presence of IA-2A at diagnosis is strongly associated with the HLA risk haplotypes, but not with PTPN22 polymorphism.