2011 Collaborative Innovation Center of Tianjin for Medical Epigenetics, Key Laboratory of Hormone and Development (Ministry of Health), Metabolic Disease Hospital & Tianjin Institute of Endocrinology, Tianjin Medical University, Tianjin 300070, China.
J Diabetes Res. 2013;2013:452537. doi: 10.1155/2013/452537. Epub 2013 Feb 26.
HLA gene system is one of the most polymorphic regions of the human genome. The association of HLA class II genes in T1DM pathogenesis has been reported for several ethnicities. Associations of HLA class II genes with T2DM have revealed inconsistent results. Moreover, correlations between DN and HLA alleles remain unclear. We carried out DNA typing chip by specific medium resolution typing probes in 310 T2DM subjects (including 210 patients with DN and 100 patients without DN) in addition to 100 healthy controls. Differences were found between patients with T2DM and the control group in the frequencies of the HLA-DQA1∗0301 (15.5% versus 8.0%, P < 0.01) and the HLA-DQA1∗0501 alleles (16.6% versus 8.5%, P < 0.01). Differences were found between patients with DN and without DN in the frequencies of the HLA-DQA1∗0302 (6.9% versus 13.5%, P < 0.01) and HLA-DQB1∗0501 alleles (5.8% versus 14.5%, P < 0.01). Diabetes duration and systolic blood pressure were independent risk factors associated with DN (OR = 2.277 and 1.366, resp., P < 0.05), whereas the HLA-DQB1∗0501 llele had a protective effect on DN (OR = 0.53, P < 0.05). These data suggest the HLA-DQA1∗0301 and HLA-DQA1∗0501 alleles are markers of susceptibility for T2DM, and the HLA-DQB1∗0501 allele is associated with a protective effect on DN in Han ethnicity of China.
HLA 基因系统是人类基因组中多态性最强的区域之一。已经报道了几种族裔的 HLA Ⅱ类基因在 T1DM 发病机制中的关联。HLA Ⅱ类基因与 T2DM 的关联结果不一致。此外，DN 与 HLA 等位基因之间的相关性仍不清楚。我们在 310 例 T2DM 患者（包括 210 例 DN 患者和 100 例无 DN 患者）和 100 例健康对照者中，使用特定的中分辨率分型探针进行了 DNA 分型芯片分析。在 T2DM 患者和对照组之间，HLA-DQA1∗0301（15.5%比 8.0%，P<0.01）和 HLA-DQA1∗0501 等位基因（16.6%比 8.5%，P<0.01）的频率存在差异。DN 患者和无 DN 患者之间，HLA-DQA1∗0302（6.9%比 13.5%，P<0.01）和 HLA-DQB1∗0501 等位基因（5.8%比 14.5%，P<0.01）的频率存在差异。糖尿病病程和收缩压是与 DN 相关的独立危险因素（OR=2.277 和 1.366，P<0.05），而 HLA-DQB1∗0501 等位基因对 DN 有保护作用（OR=0.53，P<0.05）。这些数据表明，HLA-DQA1∗0301 和 HLA-DQA1∗0501 等位基因是中国汉族人群 T2DM 的易感标志物，而 HLA-DQB1∗0501 等位基因与 DN 有保护作用。
