Berenguer Anabela Gonçalves, Fernandes Ana Teresa, Oliveira Susana, Rodrigues Mariana, Ornelas Pedro, Romeira Diogo, Serrão Tânia, Rosa Alexandra, Câmara Rita
Human Genetics Laboratory, University of Madeira, Funchal, 9000-390, Portugal.
Department of Computer Science and Engineering, University of Oulu, PL 4500, Oulu, 90014, Finland.
Biol Res. 2014 Sep 4;47(1):40. doi: 10.1186/0717-6287-47-40.
Asthma is a complex disease influenced by multiple genetic and environmental factors. While Madeira has the highest prevalence of asthma in Portugal (14.6%), the effect of both genetic and environmental factors in this population has never been assessed. We categorized 98 asthma patients according to the Global Initiative for Asthma (GINA) guidelines, established their sensitization profile, and measured their forced expiratory volume in 1 second (FEV1) and forced vital capacity (FVC) indexes. Selected single nucleotide polymorphisms (SNPs) were analysed as potential markers for asthma susceptibility and severity in the interleukin 4 (IL4), interleukin 13 (IL13), beta-2-adrenergic receptor (ADRB2), a disintegrin and metalloprotease 33 (ADAM33), gasdermin-like (GSDML) and the signal transducer and activator of transcription 6 (STAT6) genes comparatively to a population reference set.
Although mites are the major source of allergic sensitization, no significant difference was found amongst asthma severity categories. IL4-590CT/TT and IL4-RP2253183/183183 were found to predict the risk (2-fold) and severity (3 to 4-fold) of asthma and were associated with a lower FEV1 index. ADRB2-c.16AG is a risk factor (3.5-fold), while genotype GSDML-236TT was protective (4-fold) for moderate-severe asthma. ADAM33-V4C was associated to asthma and mild asthma by the transmission disequilibrium test (TDT). Finally, ADAM33-V4CC and STAT6-21*TT were associated with higher sensitization (mean wheal size ≥10 mm) to house dust (1.4-fold) and storage mite (7.8-fold).
In Madeira, IL4-590C/T, IL4-RP2 253/183, GSDML-236C/T and ADAM33-V4C/G SNPs are important risk factors for asthma susceptibility and severity, with implications for asthma healthcare management.
哮喘是一种受多种遗传和环境因素影响的复杂疾病。虽然马德拉群岛的哮喘患病率在葡萄牙最高（14.6%），但该人群中遗传和环境因素的影响从未得到评估。我们根据全球哮喘防治创议（GINA）指南对98例哮喘患者进行分类，确定他们的致敏情况，并测量他们的一秒用力呼气量（FEV1）和用力肺活量（FVC）指标。将选定的单核苷酸多态性（SNP）作为哮喘易感性和严重程度的潜在标志物，在白细胞介素4（IL4）、白细胞介素13（IL13）、β2肾上腺素能受体（ADRB2）、解整合素金属蛋白酶33（ADAM33）、gasdermin样蛋白（GSDML）和信号转导及转录激活因子6（STAT6）基因中与一组人群参考样本进行比较分析。
虽然螨是变应性致敏的主要来源，但在哮喘严重程度类别之间未发现显著差异。发现IL4-590CT/TT和IL4-RP2253183/183183可预测哮喘的风险（2倍）和严重程度（3至4倍），并与较低的FEV1指标相关。ADRB2-c.16AG是一个风险因素（3.5倍），而基因型GSDML-236TT对中重度哮喘具有保护作用（4倍）。通过传递不平衡检验（TDT），ADAM33-V4C与哮喘和轻度哮喘相关。最后，ADAM33-V4CC和STAT6-21*TT与对屋尘（1.4倍）和贮藏螨（7.8倍）的更高致敏性（平均风团大小≥10 mm）相关。
在马德拉群岛，IL4-590C/T、IL4-RP2 253/183、GSDML-236C/T和ADAM33-V4C/G SNP是哮喘易感性和严重程度的重要风险因素，对哮喘医疗管理具有重要意义。
