As β2-adrenoceptors (AR) play an important role in the regulation of bronchial smooth muscle tone, finding an association between the functional variation in the β2-AR gene and lung function would be expected. In the Australian unselected cohort, arginine (Arg) 16 was found to be associated with decreased lung function in children aged 11 yrs who had been exposed to passive smoking 1. However, in the UK high-risk cohort (at least one atopic parent), no similar association was found for 10-yr-old children 2. Arg16 was found to be associated with decreased neonatal lung function as measured by maximum flow at functional residual capacity (V′max,FRC) in the UK cohort 2. We also measured V′max,FRC in the Australian population at age 1 month. As we have previously reported 3, V′max,FRC appeared to be lower in individuals homozygous for Arg16, although this difference was not statistically significant. We agree with N.M. Wilson and A. Bush that an, as yet unknown, environmental difference between the Australian and UK cohorts that affects the in utero environment may contribute to these inconsistencies.
With regard to the relationship between β2-AR polymorphisms and exhaled nitric oxide (eNO), we surmised that there were indirect links between β2-AR and eNO through cytokine regulation or endothelial l-arginine/nitric oxide pathway 1. Interestingly, in the UK cohort, Arg16 and Glutamine (Gln) 27 were also found to be associated with decreased eNO. This finding in the UK cohort confirms the effects of β2-AR on eNO in the Australian cohort. More studies need to be conducted in order to elucidate the association between β2-AR and eNO with respect to pathogenesis of asthma and allergy.
We were interested in the comments of N.M. Wilson and A. Bush as, although there are some differences between the findings of the two birth cohort studies, the similarities are quite striking and strengthen the case that β2-adrenoceptor polymorphisms play an important role in determining phenotypic features in early life.
Statement of interest
None declared.
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