β2-肾上腺素能受体单倍型/多态性与哮喘表型之间的关联
[Association between beta2-adrenergic receptor haplotype/polymorphisms and asthma phenotype].
作者信息
Qiu Yu-Ying, Yin Kai-Sheng
机构信息
Department of Respiratory Medicine, The First Affiliated Hospital of Nanjing Medical University, Nanjing 210029, China.
出版信息
Zhonghua Jie He He Hu Xi Za Zhi. 2008 Mar;31(3):201-5.
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.
目的
分析β2 - 肾上腺素能受体（β2 - AR）基因单核苷酸多态性（SNP）/单倍型与支气管扩张剂反应及血清总免疫球蛋白E（IgE）之间的关联。
方法
采用直接DNA测序法测定201例哮喘患者和276例对照者β2 - AR基因的5个SNP（位置分别为：-47、-20、46、79、252）基因型，并于2006年2月至2007年2月组合单倍型。使用SPSS 11.5软件进行统计分析。通过卡方拟合优度分析检验每种多态性的基因型频率是否偏离哈迪 - 温伯格平衡。采用卡方检验比较5种多态基因型的频率，并通过费舍尔精确检验分析这些多态位点之间的连锁不平衡程度。对于不同基因型/单倍型之间数量性状的比较，采用方差分析。若有统计学意义，则使用最小显著差异法（LSD）。
结果
携带Argl6Argl6的患者支气管扩张剂反应为（13±4）L，显著高于携带Arg16Gly16的患者[（7±3）L]和携带Gly16Gly16的患者（7±3）L，F = 81.55，P < 0.01]。分析β2 - AR单倍型时，携带单倍型Arg16Gln27/Arg16Gln27的患者支气管扩张剂反应最高[（13.4±3.5）L]，相比之下，携带Gly16Gln27/Gly16Gln27的患者为[（6.4±0.6）L]，携带Gly16Glu27/Gly16Glu27的患者为[（7.6±3.1）L]，携带Gly16Gln27/Gly16Glu27的患者为[（6.9±3.5）L]，携带Gly16Gln27/Arg16Gln27的患者为[（7.2±3.3）L]，携带Gly16Glu27/Arg16Gln27的患者为（7.9±2.7）L，F = 32.55，P < 0.01]。基因型为Gln27Gln27的患者血清总IgE水平为（2.51±0.33）IU/L，显著高于基因型为Gln27Glu27的患者[（2.30±0.82）IU/L，F = 3.89，P < 0.05]。携带单倍型Gly16Gln27/Arg16Gln27的患者血清总IgE水平显著最低（2.13±0.15）IU/L，相比之下，携带Arg16Gln27/Arg16Gln27的患者为（2.56±0.14）IU/L，携带Gly16Glu27/Gly16Glu27的患者为（2.40±0.16）IU/L，携带Gly16Gln27/Gly16Glu27的患者为（2.54±1.26）IU/L，携带Gly16Gln27/Arg16Gln27的患者为[（2.48±0.48）IU/L，F = 3.56，P < 0.
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