Dengue Group, National Institute of Virology, 20 A Dr. Ambedkar Road, Pune, Maharashtra, India.
Hum Immunol. 2013 May;74(5):610-7. doi: 10.1016/j.humimm.2013.01.027. Epub 2013 Feb 1.
Genes coding for human leukocyte antigen (HLA) class II molecules and tumor necrosis factor (TNF)-α are polymorphic and have been shown to influence susceptibility to infectious diseases. In the present study, HLA-DRB1, -DQB1 and TNF gene polymorphisms were investigated in 114 dengue patients (DEN) [85 dengue fever (DF) cases and 29 dengue hemorrhagic fever (DHF) cases] and 110 healthy controls (HCs) using PCR based methods. The frequencies of HLA-DRB107 allele [DF vs. DHF, P=0.0034, Pc=0.044, OR 3.79] and HLA-DRB107/15 genotype [DF vs. DHF, P=0.00071, Pc=0.038, OR 10.41] were significantly higher in DHF cases as compared to HCs and DF cases. Higher frequency of rs1800629 'G/A' genotype was observed in DHF cases as compared to DF cases. The frequency of rs1799964 'C/C' genotype of the TNF gene was found to be significantly higher in all patient groups compared to HCs [HCs vs. DEN, P=0.0054, Pc=0.0162, OR 3.57; HCs vs. DF, P=0.036, OR 2.89; HCs vs. DHF, P=0.0088, Pc=0.0240, OR 5.11]. Presence of combination of HLA-DRB107/15 with either rs1799964 'C/C' genotype or rs1800629 'G/A' genotype or both was present in 17.2% of DHF cases and 1.2% in HCs while this combination was not observed in DF cases. The results suggest that HLA-DRB107/*15 genotype in combination with TNF polymorphisms influence progression to DHF.
基因编码人类白细胞抗原 (HLA) Ⅱ类分子和肿瘤坏死因子 (TNF)-α 是多态性的，已被证明会影响传染病的易感性。在本研究中，采用基于 PCR 的方法，检测了 114 例登革热患者 (DEN) [85 例登革热 (DF) 病例和 29 例登革出血热 (DHF) 病例] 和 110 例健康对照者 (HCs) 中的 HLA-DRB1、-DQB1 和 TNF 基因多态性。与 HCs 和 DF 病例相比，DHF 病例中 HLA-DRB107 等位基因 [DF 与 DHF，P=0.0034，Pc=0.044，OR 3.79] 和 HLA-DRB107/15 基因型 [DF 与 DHF，P=0.00071，Pc=0.038，OR 10.41] 的频率明显更高。与 DF 病例相比，DHF 病例中 rs1800629‘G/A’基因型的频率更高。TNF 基因 rs1799964‘C/C’基因型的频率在所有患者组中均明显高于 HCs [HCs 与 DEN，P=0.0054，Pc=0.0162，OR 3.57；HCs 与 DF，P=0.036，OR 2.89；HCs 与 DHF，P=0.0088，Pc=0.0240，OR 5.11]。在 17.2%的 DHF 病例和 1.2%的 HCs 中存在 HLA-DRB107/15 与 rs1799964‘C/C’基因型或 rs1800629‘G/A’基因型或两者的组合，而在 DF 病例中未观察到这种组合。结果表明，HLA-DRB107/*15 基因型与 TNF 多态性的组合影响 DHF 的进展。
