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变应性鼻炎中白细胞介素-12B的基因变异

Genetic variations in interleukin-12B in allergic rhinitis.

作者信息

Wei Ping, Kou Wei, Zhang Cheng, Kang Houyong, Yao Hongbing, Tang Xinye, Wang Wu

机构信息

Department of Otolaryngology, The Children's Hospital of Chongqing Medical University, Chongqing, 136# Zhongshaner Road, Chongqing, 400014, China.

Ministry of Education Key Laboratory of Child Development and Disorders, Chongqing, China.

出版信息

Immunol Res. 2016 Feb;64(1):329-36. doi: 10.1007/s12026-015-8758-6.

Abstract

Interleukin (IL)-12B is a key regulator in the protection against allergic reaction induced by various allergens in patients with allergic rhinitis (AR). This study was performed to investigate the associations between single nucleotide polymorphisms in the IL-12B gene and AR in a Chinese Han population. A total of 543 patients with AR and 600 healthy controls were genotyped for IL-12B/rs6887695, rs10045431, rs3212227, rs3212217, and rs2082412 using polymerase chain reaction (PCR) restriction fragment length polymorphism and PCR direct sequencing. The expression of IL-12B mRNA in peripheral blood mononuclear cells (PBMCs) obtained from normal controls was detected by quantitative real-time PCR. Levels of interferon (IFN)-γ and IL-4 in culture supernatants were measured by enzyme-linked immunosorbent assay. The frequencies of the rs3212227 genotype with the CC and C alleles were higher in patients with AR (p c = 8.55 × 10(-4); p c = 4.20 × 10(-4), respectively) than in normal controls. After peptidoglycan stimulation in PBMCs, IL-12 mRNA expression was reduced in healthy carriers of the CC genotype of rs3212227. Additionally, decreased production of IFN-γ was observed in patients having the CC genotype as compared with that in patients having the AC and AA genotypes. In contrast, IL-4 expression was higher in patients with the CC genotype than in patients with the other two genotypes. The IL-12B gene was involved in mediating susceptibility to AR.

摘要

白细胞介素(IL)-12B是变应性鼻炎(AR)患者抵御各种过敏原诱发过敏反应的关键调节因子。本研究旨在探讨中国汉族人群中IL-12B基因单核苷酸多态性与AR之间的关联。采用聚合酶链反应(PCR)-限制性片段长度多态性和PCR直接测序法,对543例AR患者和600例健康对照者进行IL-12B/rs6887695、rs10045431、rs3212227、rs3212217和rs2082412基因分型。通过定量实时PCR检测正常对照者外周血单个核细胞(PBMC)中IL-12B mRNA的表达。采用酶联免疫吸附测定法检测培养上清液中干扰素(IFN)-γ和IL-4的水平。AR患者中rs3212227基因型CC和C等位基因的频率高于正常对照者(校正P值分别为8.55×10⁻⁴和4.20×10⁻⁴)。在PBMC中经肽聚糖刺激后,rs3212227基因型CC的健康携带者中IL-12 mRNA表达降低。此外,与AC和AA基因型患者相比,CC基因型患者中IFN-γ的产生减少。相反,CC基因型患者中IL-4的表达高于其他两种基因型患者。IL-12B基因参与介导AR易感性。

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