β2-adrenergic receptor polymorphisms in African American children with status asthmaticus

被引:18
作者
Elbahlawan, Lama
Binaei, Saeed
Christensen, Michael L.
Zhang, Qing
Quasney, Michael W.
Dahmer, Mary K.
机构
[1] St Jude Childrens Hosp, Memphis, TN 38105 USA
[2] Univ Tennessee, Ctr Hlth Sci, Dept Mol Sci, Memphis, TN 38163 USA
[3] Santa Barbara Cottage Hosp, Santa Barbara, CA USA
[4] Memphis Res Ctr, Childrens Fdn, Memphis, TN USA
关键词
asthma; beta(2)-adrenergic receptor; polymorphism; down regulation; pediatrics;
D O I
10.1097/01.PCC.0000194010.63115.A2
中图分类号
R4 [临床医学];
学科分类号
1002 ; 100602 ;
摘要
Background. The beta(2)-adrenergic receptor plays a central role in the bronchodilator response to beta(2)-agonists in patents with asthma. Genetic polymorphisms within the gene coding for this receptor influence responsiveness of the receptor. A number of these polymorphisms differ in frequency in the African American and white populations. Objective: To determine the frequency of specific beta(2)-adrenergic receptor polymorphisms in African American children with status asthmaticus and to examine whether a specific genotype is associated with the clinical response to therapy. Design: Cohort of African American children diagnosed with status asthmaticus. Setting. Tertiary care children's hospital. Patients., A total of 31 African American children with status asthmaticus. Intervention. Blood samples were obtained from children at admission. Genotypes were determined by polymerase chain reaction amplification and restriction enzyme digestion. Main Outcome Measures: The requirement for admission to the pediatric intensive care unit, need for mechanical ventilation, institution of various therapies, and length of stay. Results. The genotypes of the polymorphic sites at amino acid positions 16 and 27 in the beta(2)-adrenergic receptor were determined. There were no significant differences between the various genotypes in the percentage of children requiring pediatric intensive care unit admission, mechanical ventilation, terbutaline treatment or length of stay. However, in children heterozygous for Glu at position 27 of the beta(2)-adrenergic receptor, the percentage of patents requiring aminophylline treatment in addition to beta(2)-agonist therapy, was significantly higher than that seen in patients homozygous for Gin at that position (5/10 [50%] vs. 1/21 [5%], respectively; p =.002). Conclusions. African American children with status asthmaticus who have the Gln/Glu genotype at amino acid position 27 of the beta(2)-adrenergic receptor may benefit from aminophylline treatment in addition to beta(2)-agonist therapy.
引用
收藏
页码:15 / 18
页数:4
相关论文
共 13 条
[1]  
Aynacioglu AS, 1999, BRIT J CLIN PHARMACO, V48, P761
[2]   RECENT ADVANCES IN ASTHMA [J].
BARNES, PJ ;
LEE, TH .
POSTGRADUATE MEDICAL JOURNAL, 1992, 68 (806) :942-953
[3]   Race, asthma, and persistent wheeze in Philadelphia schoolchildren [J].
Cunningham, J ;
Dockery, DW ;
Speizer, FE .
AMERICAN JOURNAL OF PUBLIC HEALTH, 1996, 86 (10) :1406-1409
[4]   Heterogeneity of therapeutic responses in asthma [J].
Drazen, JM ;
Silverman, EK ;
Lee, TH .
BRITISH MEDICAL BULLETIN, 2000, 56 (04) :1054-1070
[5]   Complex promoter and coding region β2-adrenergic receptor haplotypes alter receptor expression and predict in vivo responsiveness [J].
Drysdale, CM ;
McGraw, DW ;
Stack, CB ;
Stephens, JC ;
Judson, RS ;
Nandabalan, K ;
Arnold, K ;
Ruano, G ;
Liggett, SB .
PROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, 2000, 97 (19) :10483-10488
[6]   INFLUENCE OF BETA(2)-ADRENERGIC RECEPTOR GENOTYPES ON SIGNAL-TRANSDUCTION IN HUMAN AIRWAY SMOOTH-MUSCLE CELLS [J].
GREEN, SA ;
TURKI, J ;
BEJARANO, P ;
HALL, IP ;
LIGGETT, SB .
AMERICAN JOURNAL OF RESPIRATORY CELL AND MOLECULAR BIOLOGY, 1995, 13 (01) :25-33
[7]   Polymorphisms of the 5′ leader cistron of the human β2-adrenergic receptor regulate receptor expression [J].
McGraw, DW ;
Forbes, SL ;
Kramer, LA ;
Liggett, SB .
JOURNAL OF CLINICAL INVESTIGATION, 1998, 102 (11) :1927-1932
[8]   Polymorphism of the β2-adrenergic receptor gene and desensitization in human airway smooth muscle [J].
Moore, PE ;
Laporte, JD ;
Abraham, JH ;
Schwartzman, IN ;
Yandava, CN ;
Silverman, ES ;
Drazen, JM ;
Wand, MP ;
Panettieri, RA ;
Shore, SA .
AMERICAN JOURNAL OF RESPIRATORY AND CRITICAL CARE MEDICINE, 2000, 162 (06) :2117-2124
[9]   DRUG-THERAPY - BETA-ADRENERGIC BRONCHODILATORS [J].
NELSON, HS .
NEW ENGLAND JOURNAL OF MEDICINE, 1995, 333 (08) :499-506
[10]   Relationships of race and socioeconomic status with prevalence, severity, and symptoms of asthma in Chicago school children [J].
Persky, VW ;
Slezak, J ;
Contreras, A ;
Becker, L ;
Hernandez, E ;
Ramakrishnan, V ;
Piorkowski, J .
ANNALS OF ALLERGY ASTHMA & IMMUNOLOGY, 1998, 81 (03) :266-271