A sequence variant on 17q21 is associated with age at onset and severity of asthma

作者：Halapi Eva; Gudbjartsson Daniel F; Jonsdottir Gudrun M; Bjornsdottir Unnur S; Thorleifsson Gudmar; Helgadottir Hafdis; Williams Carolyn; Koppelman Gerard H; Heinzmann Andrea; Boezen H Marike; Jonasdottir Aslaug; Blondal Thorarinn; Gudjonsson Sigurjon A; Jonasdottir Adalbjorg; Thorlacius Theodora; Henry Amanda P; Altmueller Janine; Krueger Marcus; Shin Hyoung Doo; Uh Soo Taek; Cheong Hyun Sub; Jonsdottir Brynja; Ludviksson Bjorn R; Ludviksdottir Dora

来源：European Journal of Human Genetics, 2010, 18(8): 902-908.

DOI：10.1038/ejhg.2010.38

• childhood asthma
• single-nucleotide polymorphism
• expression
• ORMDL3
• GSDMB

A sequence variant (rs7216389-T) near the ORMDL3 gene on chromosome 17q21 was recently found to be associated with childhood asthma. We sought to evaluate the effect of rs7216389-T on asthma subphenotypes and its correlation with expression levels of neighboring genes. The association of rs7216389-T with asthma was replicated in six European and one Asian study cohort (N=4917 cases N=34 589 controls). In addition, we found that the association of rs7216389-T was confined to cases with early onset of asthma, particularly in early childhood (age: 0-5 years OR=1.51, P=6.89. 10(-9)) and adolescence (age: 14-17 years OR=1.71, P=5.47. 10(-9)). A weaker association was observed for onset between 6 and 13 years of age (OR=1.17, P=0.035), but none for adult-onset asthma (OR=1.07, P=0.12). Cases were further stratified by sex, asthma severity and atopy status. An association with greater asthma severity was observed among early-onset asthma cases (P=0.0012), but no association with sex or atopy status was observed among the asthma cases. An association between sequence variants and the expression of genes in the 17q21 region was assessed in white blood cell RNA samples collected from Icelandic individuals (n=743). rs7216389 associated with the expression of GSDMB and ORMDL3 genes. However, other sequence variants showing a weaker association with asthma compared with that of rs7216389 were more strongly associated with the expression of both genes. Thus, the contribution of rs7216389-T to the development of asthma is unlikely to operate only through an impact on the expression of ORMDL3 or GSDMB genes.
European Journal of Human Genetics (2010) 18, 902-908; doi:10.1038/ejhg.2010.38; published online 7 April 2010

• 出版日期2010-8
• 单位河北医科大学