Association of SERPINE2 with Asthma by Himes Blanca E, Klanderman Barbara, Ziniti John, Senter-Sylvia Jody, Soto-Quiros Manuel E, Avila Lydiana, Celedón Juan C, Lange Christoph, Mariani Thomas J, Lasky-Su Jessica, Hersh Craig P, Raby Benjamin A, Silverman Edwin K, Weiss Scott T, Demeo Dawn L in Chest (2011).

[PMID: 21436250] PubMed


Abstract BACKGROUND: The "Dutch hypothesis" suggests that asthma and COPD have common genetic determinants. SERPINE2 is a gene that has been previously associated with COPD. We sought to determine whether SERPINE2 is associated with asthma and asthma-related phenotypes. METHODS: We measured the association of 39 SERPINE2 single nucleotide polymorphisms (SNPs) with asthma-related phenotypes in 655 parent-child trios of the Childhood Asthma Management Program, and we measured the association of 19 SERPINE2 SNPs with asthma in a case-control design of 359 CAMP probands and 846 population controls. We attempted to replicate primary asthma-related phenotype findings in one independent population and primary asthma affection status findings in two independent populations. We compared association results with CAMP proband expression quantitative trait loci (eQTL). RESULTS: Nine of 39 SNPs had p-values <0.05 for at least one phenotype in CAMP, and two of these replicated in an independent population of 426 childhood asthmatics. Six of 19 SNPs had p-values <0.05 for association with asthma in CAMP/Illumina. None of these replicated in two independent populations. The eQTL revealed that five SNPs associated with asthma in CAMP/Illumina and one SNP associated with FEV(1) in CAMP are strongly correlated with SERPINE2 expression levels. Comparison of results to previous COPD studies identified five SNPs that have been associated with both asthma- and COPD-related phenotypes. CONCLUSIONS: Our results weakly support SERPINE2 as a Dutch Hypothesis candidate gene via nominally significant associations with asthma and related traits. Further study of SERPINE2 is necessary to verify its involvement in asthma and COPD.

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