Pampuch A, Kowal K, Bodzenta-Lukaszyk A, Di Castelnuovo A, Chyczewski L, Donati M B, Iacoviello L
Department of Allergology and Internal Medicine, Medical University of Bialystok, Bialystok, Poland.
Allergy. 2006 Feb;61(2):234-8. doi: 10.1111/j.1398-9995.2005.00948.x.
Plasminogen activator inhibitor (PAI)-1 plays an important role in inflammation and tissue remodeling. Recently, the -675 4G/5G PAI-1 polymorphism has been linked with asthma.
This study was undertaken to evaluate associations of the -675 4G/5G PAI-1 polymorphism with functional and immunologic parameters of newly diagnosed house dust mite-sensitive allergic asthmatics (HDM-AAs).
This study was performed in 127 HDM-AAs, who responded with at least 20% fall of forced expiratory volume during the first second (FEV(1)) to a bronchial challenge with Dermatophagoides pteronyssinus allergen and during the follow up observation fulfilled GINA criteria for mild-moderate asthma. About 89 healthy control nonatopic subjects (HCs) were used as controls.
The frequency of 4G allele was greater in HDM-AAs (0.69; 95% CI: 0.62-0.76) than in HCs (0.55; 95% CI: 0.48-0.62; P = 0.0034). The PAI-1 polymorphism was associated with an increased risk of HDM-AA; adjusted for sex and age odds ratio was 2.62; (95% CI: 1.16-5.92) for 4G/5G genotype and 3.48 (95% CI: 1.54-7.89) for 4G/4G genotype compared with 5G/5G genotype. Total serum immunoglobulin E (tsIgE) level in 4G/4G homozygotes (557 +/- 343 kU/l) was significantly greater than in 5G/5G homozygotes (241 +/- 288 kU/l; P < 0.001). Both nonspecific and allergen-specific bronchial reactivities were greater in 4G/4G homozygotes than in 5G/5G homozygotes. 4G/4G genotype was associated with significantly higher morning plasma PAI-1 concentration in HDM-AAs and HCs. Morning plasma PAI-1 concentration correlated significantly with log(PC20) (r = -0.39; P = 0.0001) and with log(tsIgE) (r = 0.247; P = 0.0117).
These results support the hypothesis linking the 4G/4G PAI-1 genotype with an increased risk of allergic asthma, bronchial hyperreactivity, and increased tsIgE levels.
纤溶酶原激活物抑制剂（PAI）-1在炎症和组织重塑中起重要作用。最近，-675 4G/5G PAI-1基因多态性与哮喘相关。
本研究旨在评估-675 4G/5G PAI-1基因多态性与新诊断的屋尘螨敏感型过敏性哮喘患者（HDM-AAs）的功能和免疫参数之间的关联。
本研究纳入了127例HDM-AAs患者，这些患者在首次接受粉尘螨变应原支气管激发试验时第一秒用力呼气容积（FEV(1)）至少下降20%，且在随访观察期间符合轻度至中度哮喘的GINA标准。约89名健康对照非特应性受试者（HCs）用作对照。
HDM-AAs患者中4G等位基因频率（0.69；95%CI：0.62-0.76）高于HCs（0.55；95%CI：0.48-0.62；P = 0.0034）。PAI-1基因多态性与HDM-AA风险增加相关；调整性别和年龄后，4G/5G基因型的优势比为2.62；（95%CI：1.16-5.92），4G/4G基因型与5G/5G基因型相比为3.48（95%CI：1.54-7.89）。4G/4G纯合子的总血清免疫球蛋白E（tsIgE）水平（557±343 kU/l）显著高于5G/5G纯合子（241±288 kU/l；P < 0.001）。4G/4G纯合子的非特异性和变应原特异性支气管反应性均高于5G/5G纯合子。4G/4G基因型与HDM-AAs患者和HCs患者早晨血浆PAI-1浓度显著升高相关。早晨血浆PAI-1浓度与log(PC20)（r = -0.39；P = 0.0001）和log(tsIgE)（r = 0.247；P = 0.0117）显著相关。
这些结果支持将4G/4G PAI-1基因型与过敏性哮喘风险增加、支气管高反应性和tsIgE水平升高相关联的假设。
