ABCMdb

PMID: 12142724

Buscher R, Eilmes KJ, Grasemann H, Torres B, Knauer N, Sroka K, Insel PA, Ratjen F
beta2 adrenoceptor gene polymorphisms in cystic fibrosis lung disease.
Pharmacogenetics. 2002 Jul;12(5):347-53., [PubMed]

Sentences

No. Mutations Sentence Comment

18 ABCC7 p.Thr164Ile Nine different polymorphic loci in the â2AR gene have been identified, of which four change the amino acid sequence of the â2AR protein: Arg16 Gly, Gln27 Glu, Val34 Met and Thr164 Ile [12]. Login to comment 20 ABCC7 p.Thr164Ile The only genetic variant that leads to a decreased binding of agonist is the Thr164 Ile polymorphism which is rare (, 5%) and has been found only in heterozygous form [12]. Login to comment 32 ABCC7 p.Thr164Ile Subjects were analysed according to their genotype for the Arg16 Gly, Gln27 Glu and Thr164 Ile alleles. Login to comment 33 ABCC7 p.Thr164Ile Patients with the genotype Arg16 Arg, Gln27 Gln and Thr164 Thr carry the wild-type alleles, Arg16 Gly, Gln27 Glu and Thr164 Ile are heterozygous for the alleles and individuals with the Gly16 Gly or Glu27 Glu genotype are homozygous for the respective polymorphic allele. Login to comment 45 ABCC7 p.Thr164Ile The primers used for detection of the Thr164 Ile polymorphism were forward primer (59- GTGATCGCAGTGGATCGCTACT-39) and reverse primer (59-AGAGCAAGACCATGATCACCAG-39), and an annealing temperature of 58 8C was used. Login to comment 76 ABCC7 p.Thr164Ile The frequency of the Thr164 Ile polymorphism is below 5% within different populations [10,11,14] and, in our study, was only detected in four cystic fibrosis patients in heterozygous form. Login to comment 83 ABCC7 p.Thr164Ile Isoproterenol-stimulated cAMP formation, expressed as percentage of basal stimulation, was significantly decreased in patients heterozygous for the Thr164 Ile polymorphism compared to four subjects homozygous for Arg16 , Gln27 and Thr164 (P ¼ 0.0013) (Fig. 3). Login to comment 84 ABCC7 p.Thr164Ile cAMP formation in subjects double-heterozygous for Arg16 Gly and Gln27 Glu was similar to that of subjects who had the Thr164 Ile polymorphism (Fig. 3). Login to comment 104 ABCC7 p.Thr164Ile Similarly, patients homozygous for the Thr164 allele have significantly higher values for FVC, FEV1 and MEF50 when compared to heterozygous allele carriers (Thr164 Ile). Login to comment 105 ABCC7 p.Thr164Ile 100 50 0 %predicted FVC FEV1 MEF50% Thr164Thr Thr164Ile * * * 100 75 50 -4 -3 -2 -1 0 Time (year) FEV1(%predicted) * Arg16Arg n ϭ 22 Arg16 Gly ϩ Gly16 Gly n ϭ 37 Fig. 2 Evolution of pulmonary function, expressed as decline in FEV1 in percentage predicted, over 5 years in 59 cystic fibrosis patients. Login to comment 107 ABCC7 p.Thr164Ile ABCC7 p.Thr164Ile 1000 500 0 -10 -9 -8 -7 -6 -log[iso] cAMPformation (%ofbasal) CF Thr164 Ile CF Arg16 Arg ϩ CF Gln27 Gln ϩ CF Thr164 Thr CF Arg16 Gly ϩ CF Gln27 Glu ϩ CF Thr164 Thr n ϭ 3 n ϭ 4 n ϭ 4 * Fig. 3 Isoproterenol-induced cyclic AMP formation in four cystic fibrosis patients, each of whom were either heterozygous for Thr164 Ile (j), homozygous for Thr164 , Arg16 and Gln27 (m), or heterozygous for Arg16 Gly and Gln27 Glu but homozygous for Thr164 (.). Login to comment