Association between β₂-adrenoceptor polymorphisms and asthma diagnosis among Mexican adults - 29/08/11

Doi : 10.1016/j.jaci.2003.09.029

Alfredo A Santillan, MD, MPH ^a,^b, Carlos A Camargo, MD, DrPH ^c,^⁎, Alicia Ramirez-Rivera, MD ^b, Ivan Delgado-Enciso, MD ^a, Augusto Rojas-Martinez, MD ^a, Felipe Cantu-Diaz, MD ^b, Hugo A Barrera-Saldaña, MD ^a
^a Departamento de Bioquímica, Facultad de Medicina, Universidad Autónoma de Nuevo León (UANL), Monterrey, México
^b Laboratorio de Fisiología Pulmonar, Hospital de Enfermedades Cardiovasculares y del Tórax, Centro Médico Nacional del Norte, Instituto Mexicano del Seguro Social (IMSS), Monterrey, México
^c Channing Laboratory, Department of Medicine, Brigham and Women's Hospital, and the Department of Emergency Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, Mass, USA

Reprint requests: Dr Carlos A. Camargo, Jr, Massachusetts General Hospital, 55 Fruit St, Clinics Bldg 397, Boston, MA, 02114-2969

Abstract

Background

Recent studies demonstrate that genetic variations in the human β₂-adrenergic receptor (β₂AR) structure at codons 16 and 27 alter receptor function in vitro and are associated with asthma severity and airway hyperresponsiveness but have not been linked to asthma diagnosis. The nature of the relation in a more homogeneous population is uncertain.

Objective

We determined frequencies of these polymorphisms to explore the association between β₂AR haplotypes and asthma diagnosis and phenotype.

Methods

This is a population-based, case-control study that involves a total sample of 907 unrelated Mexican Mestizos. Genotyping at β₂AR was identified by polymerase chain reaction–restriction fragment length polymorphism analysis. Multivariate logistic regression analysis was used to estimate the odds ratio (OR) of the association between β₂AR haplotype status and asthma diagnosis.

Results

A significant inverse association was found between subjects with Glu27 allele (OR, 0.5; 95% CI, 0.4 to 0.7) and Gly16-Glu27 alleles (OR, 0.5; 95% CI, 0.3 to 0.8) and asthma. Sex differences in this association were explored, given the complex relation between sex and asthma. Among men, a positive association was present between the “Gly16 allele without Glu27” (OR, 2.9; 95% CI, 1.26 to 6.8) and asthma. In contrast, a lower risk of asthma was found among women Gly16-Glu27 alleles (OR, 0.3; 95% CI, 0.2 to 0.6). Nocturnal asthma was associated with the Gly16 allele (OR, 1.8; 95% CI, 1.3 to 2.6).