Alpha-1 Antitrypsin Gene Variants in Patients without Severe Deficiency Diagnosed with Pulmonary Emphysema on Chest CT

Abstract

Eduardo Laviña,1,2 Sara Lumbreras,3 Lara Bravo,4 Joan B Soriano,5 José Luis Izquierdo,1,6 Jose Miguel Rodríguez4,6 1Servicio de Neumología, Hospital Universitario de Guadalajara, Guadalajara, Spain; 2Escuela de Doctorado, Programa Doctoral en Ciencias de la Salud, Universidad de Alcalá, Alcalá de Henares, Madrid, Spain; 3Departamento de Organización Industrial, Escuela Técnica Superior de Ingeniería (ICAI), Universidad Pontificia Comillas – IIT, Madrid, Spain; 4Servicio de Neumología, Hospital Universitario Príncipe de Asturias, Alcalá de Henares, Madrid, Spain; 5Servicio de Neumología, Hospital Universitario de la Princesa; Facultad de Medicina, Universidad Autónoma de Madrid; and Centro de Investigación Biomédica En Red de Enfermedades Respiratorias (CIBERES), Instituto de Salud Carlos III; All in Madrid, Madrid, Spain; 6Departamento de Medicina y Especialidades Médicas, Universidad de Alcalá, Alcalá de Henares, Madrid, SpainCorrespondence: José Luis Izquierdo, Servicio de Neumología, Hospital Universitario de Guadalajara, Calle Donantes de Sangre, Guadalajara, SN, 19002, Spain, Email [email protected]: Although pulmonary involvement due to alpha-1 antitrypsin (AAT) deficiency has been widely described, most studies focus on the genotypes causing severe deficiency (< 60 mg/dL).Objective: The aim of this study was to analyze the prevalence of the different AAT gene variants that do not cause severe deficiency in patients with pulmonary emphysema diagnosed by thoracic computed tomography (CT). Furthermore, we assessed the risk associated with a non-severe decrease in AAT values in the pathogenesis of emphysema.Methods: Case-control study design that included patients who had a CT scan available of the entire thorax. In total, 176 patients with emphysema (cases) and 100 control subjects without emphysema were analyzed.Results: The prevalence of variants was higher among cases (25.6%; 45/176) than controls (22%; 22/100), although the difference was not statistically significant (P=0.504) when analyzed globally. In the control group, all the variants detected were MS. Excluding this variant, statistically significant differences were observed in the remaining variants (MZ, SS and SZ). Only 18% of the controls (all MS) presented values below our limit of normality, and all had values very close to the reference value (90 mg/dL). In contrast, 76% of patients with the other variants presented pathological levels. In a logistic regression model, both smoking and a non-severe reduction in AAT (60 to 90 mg/dL) increased the probability of emphysema.Conclusion: Our study confirms an association between certain variants in the alpha-1 antitrypsin gene that do not cause severe deficiency and the presence of pulmonary emphysema. This association with variants that are associated with reductions in serum AAT values is statistically significant and independent of smoking habit.Keywords: emphysema, alpha-1 antitrypsin, deficiency, variants

Keywords

• emphysema
• alpha-1 antitrypsin
• deficiency
• variants