Mahdaviani Seyed Alireza, Rezaei Nima, Moradi Batoul, Dorkhosh Shahin, Amirzargar Ali Akbar, Movahedi Masoud
Department of Allergy and Clinical Immunology, Children's Medical Center Hospital, Immunology, Asthma, and Allergy Research Institute, Tehran University of Medical Sciences, 62 Gharib St, Keshavarz Blvd, P. O. Box 14185-863, Tehran, 14194, Iran.
J Clin Immunol. 2009 Jan;29(1):57-62. doi: 10.1007/s10875-008-9232-1. Epub 2008 Sep 2.
Asthma is one of the most common respiratory diseases caused by acute and chronic inflammation of airways. Proinflammatory cytokines could contribute to this inflammatory process. This study was performed in order to analyze the genetic profile of proinflammatory cytokines in Iranian asthmatic patients.
The allele and genotype frequencies of a number polymorphic genes coding for tumor necrosis factor (TNF)-alpha, interleukin (IL)-1 alpha, IL-1 beta, IL-1 receptor (IL-1R), IL-1RA, and IL-6 were investigated in 60 patients with asthma in comparison with 140 controls using polymerase chain reaction with sequence-specific primers.
The most frequent genotypes in our patients were TNF-alpha GA at position -308 (P = 0.001), TNF-alpha AA at position -238 (P = 0.01), IL-1 alpha TC at position -889 (P = 0.0001), IL-1 beta TC at position -511 (P = 0.0001), and IL-1RA TC at position Mspa-I 11100 (P = 0.001). In contrast, the frequencies of the genotypes TNF-alpha GG at position -308 (P = 0.001), IL-1 alpha CC at position -889 (P = 0.005), IL-1 beta CC at position -511 (P = 0.0001), and IL-1RA TT at position Mspa-I 11100 (P = 0.0001) in the patient group were significantly lower than controls. The most frequent haplotypes for TNF-alpha (positions 308, -238) was A/A in the patient group in comparison with controls (P = 0.0001).
While environmental factors are important in the development of asthma, genetic factors could have a critical role in the expression of the disease. Considering the high frequency of presence of TNF-alpha AG genotype (-308), it seems that the production of TNF-alpha in the asthmatic patients could be higher than normal subjects.
哮喘是由气道急慢性炎症引起的最常见的呼吸系统疾病之一。促炎细胞因子可能参与了这一炎症过程。本研究旨在分析伊朗哮喘患者促炎细胞因子的基因谱。
采用序列特异性引物聚合酶链反应,对60例哮喘患者和140例对照者编码肿瘤坏死因子(TNF)-α、白细胞介素(IL)-1α、IL-1β、IL-1受体(IL-1R)、IL-1受体拮抗剂(IL-1RA)和IL-6的多个多态性基因的等位基因和基因型频率进行了研究。
患者中最常见的基因型为TNF-α -308位点的GA(P = 0.001)、TNF-α -238位点的AA(P = 0.01)、IL-1α -889位点的TC(P = 0.0001)、IL-1β -511位点的TC(P = 0.0001)和IL-1RA Mspa-I 11100位点的TC(P = 0.001)。相反,患者组中TNF-α -308位点的GG(P = 0.001)、IL-1α -889位点的CC(P = 0.005)、IL-1β -511位点的CC(P = 0.0001)和IL-1RA Mspa-I 11100位点的TT(P = 0.0001)基因型频率显著低于对照组。与对照组相比,患者组中TNF-α(-308、-238位点)最常见的单倍型为A/A(P = 0.0001)。
虽然环境因素在哮喘的发生发展中很重要,但遗传因素在该疾病的表达中可能起关键作用。考虑到TNF-α AG基因型(-308)的高频率存在,似乎哮喘患者中TNF-α的产生可能高于正常受试者。