[Association between beta2-adrenergic receptor haplotype/polymorphisms and asthma phenotype].
OBJECTIVE
To analyze the association of single nucleotide polymorphisms (SNP)/ haplotypes of beta2-adrenergic receptor (beta2-AR) gene with bronchodilator response and total serum immunoglobulin E (IgE).


METHODS
Five SNP (in positions: -47, -20, 46, 79, 252) genotypes of beta2-AR gene in 201 asthmatic patients and 276 controls were determined by direct DNA sequencing, and the haplotypes were combined from 2006 February to 2007 February. Statistical analyses were performed with SPSS 11.5 software. The genotype frequencies for each polymorphism were tested for deviation from the Hardy-Weinberg equilibrium by chi2 goodness-of-fit analysis. The frequencies of the five polymorphic genotypes were compared with chi2 test, and the degree of linkage disequilibrium occurring between these polymorphic loci were analyzed by fisher' s exact. For the comparison of quantitative traits among different genotypes/haplotypes, ANOVA was used. Least significant difference (LSD) was used if there was statistical significant.


RESULTS
The bronchodilator response in patients with Argl6Argl6 was (13 +/- 4)L, significantly higher than those with Arg16Gly16 [(7 +/- 3) L and Gly16Gly16 (7 +/- 3)L, F = 81.55, P < 0.01]. When beta2-AR haplotypes were analyzed, bronchodilator response was highest in patients with haplotype Arg16Gln27/Arg16Gln27 [(13.4 +/- 3.5) L], compared to that with Gly16Gln27/Gly16Gln27 [(6.4 +/- 0.6) L], Gly16Glu27/Gly16Glu27 [(7.6 +/- 3.1)L], Gly16Gln27/Gly16Glu27 [(6.9 +/- 3.5)L], Gly16Gln27/Arg16Gln27 [(7.2 +/- 3.3) L, and Gly16Glu27/Arg16Gln27 (7.9 +/- 2.7) L, F = 32.55, P < 0.01]. The total IgE level was (2.51 +/- 0.33) IU/L in patients with genotype Gln27Gln27, significantly higher than that with Gln27Glu27 [(2.30 +/- 0.82) IU/L, F = 3.89, P < 0.05]. The total IgE level was significantly lowest in patients with haplotype Gly16Gln27/Arg16Gln27 (2.13 +/- 0.15) IU/L, compared to that with Arg16Gln27/Arg16Gln27 (2.56 +/- 0.14) IU/L, Gly16Glu27/Gly16Glu27 (2.40 +/- 0.16) IU/L, Gly16Gln27/Gly16Glu27 (2.54 +/- 1.26) IU/L, Gly16Gln27/Arg16Gln27 [(2.48 +/- 0.48) IU/L, F = 3.56, P < 0.01].


CONCLUSIONS
These results indicate that depending on phenotypes studied, either an individual beta2-AR SNP or haplotype might affect disease manifestations.
Qiu
Yu-Ying
YY
Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
Yin
Kai-Sheng
KS
D000328:Adult; D001249:Asthma / Q000235:genetics*; D016022:Case-Control Studies; D005260:Female; D006239:Haplotypes; D006801:Humans; D008297:Male; D008875:Middle Aged; D010641:Phenotype; D020641:Polymorphism, Single Nucleotide; D018343:Receptors, Adrenergic, beta-2 / Q000235:genetics*
D018343:Receptors, Adrenergic, beta-2