Törn Carina, Hillman Magnus, Sanjeevi Carani B, Landin-Olsson Mona
Diabetes Laboratory, Institution of Clinical Sciences, Lund University, Lund, Sweden.
Hum Immunol. 2006 Jul;67(7):527-34. doi: 10.1016/j.humimm.2006.04.002. Epub 2006 May 9.
We explored the importance of the genetic markers microsatellite TNFa, HLA-DR3-DQ2, and DR4-DQ8 in diabetes mellitus. The studied groups comprised autoimmune type 1 (n = 63), nonautoimmune type 1 (n = 35), latent autoimmune diabetes in adults (LADA; n = 54), and nonautoimmune type 2 (n = 340) and these patients were compared to 117 healthy controls. HLA genotyping was done with polymerase chain reaction and sequence-specific oligonucleotides. TNFa microsatellites were determined with polymerase chain reaction and fragment size determination. Univariate analysis of these genetic risk factors demonstrated that homozygosity for TNFa2/2 was a significant risk factor for autoimmune type 1 diabetes (odds ratio (OR) = 5.82; 95% confidence interval (95%CI) 1.97-17.2), for autoimmune negative type 1 diabetes (OR = 4.63; 95%CI 1.32-16.2), and for LADA (OR = 3.90; 95%CI 1.21-12.5). Moreover, heterozygosity for HLA-DR3-DQ2/DR4-DQ8 was an important risk factor for autoimmune type 1 diabetes (OR = 16.4; 95%CI 3.60-75) as was DR4-DQ8/x (OR = 2.52; 95%CI 1.27-4.98). Heterozygosity for HLA-DR3-DQ2/DR4-DQ8 was a risk factor also for LADA (OR = 10.0; 95%CI 2.05-48.9). Neither HLA-DR3-DQ2 nor DR4-DQ8 were risk factors for nonautoimmune type 1 or type 2 diabetes. We concluded that heterozygosity for DR3-DQ2/DR4-DQ8 and to some extent homozygosity for TNFa2/2 were risk factors for autoimmune diabetes irrespective of the clinical classification.
我们探究了基因标记微卫星肿瘤坏死因子α（TNFα）、人类白细胞抗原DR3-DQ2以及DR4-DQ8在糖尿病中的重要性。研究组包括自身免疫性1型糖尿病患者（n = 63）、非自身免疫性1型糖尿病患者（n = 35）、成人隐匿性自身免疫性糖尿病（LADA；n = 54）以及非自身免疫性2型糖尿病患者（n = 340），并将这些患者与117名健康对照者进行比较。采用聚合酶链反应和序列特异性寡核苷酸进行HLA基因分型。通过聚合酶链反应和片段大小测定来确定TNFα微卫星。对这些遗传风险因素进行单因素分析表明，TNFα2/2纯合子是自身免疫性1型糖尿病的显著风险因素（优势比（OR）= 5.82；95%置信区间（95%CI）1.97 - 17.2），是非自身免疫性阴性1型糖尿病的风险因素（OR = 4.63；95%CI 1.32 - 16.2），也是LADA的风险因素（OR = 3.90；95%CI 1.21 - 12.5）。此外，HLA-DR3-DQ2/DR4-DQ8杂合子是自身免疫性1型糖尿病的重要风险因素（OR = 16.4；95%CI 3.60 - 75），DR4-DQ8/x也是（OR = 2.52；95%CI 1.27 - 4.98）。HLA-DR3-DQ2/DR4-DQ8杂合子也是LADA的风险因素（OR = 10.0；95%CI 2.05 - 48.9）。HLA-DR3-DQ2和DR4-DQ8都不是非自身免疫性1型或2型糖尿病的风险因素。我们得出结论，DR3-DQ2/DR4-DQ8杂合子以及在一定程度上TNFα2/2纯合子是自身免疫性糖尿病的风险因素，与临床分类无关。
