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Acute Asthma in Children

Relationships among CD14 and CC16 Genotypes, Plasma Levels, and Severity

Andrew C. Martin, Ingrid A. Laing, Siew-Kim Khoo, Guicheng Zhang, Kristina Rueter, Laurel Teoh, Shahir Taheri, Catherine M. Hayden, Gary C. Geelhoed, Jack Goldblatt and Peter N. LeSouëf

School of Paediatrics and Child Health, University of Western Australia, Perth, Western Australia, Australia

Correspondence and requests for reprints should be addressed to Andrew Martin, M.B.B.S., M.R.C.P., Princess Margaret Hospital for Children, Roberts Road, Subiaco, Western Australia 6008, Australia. E-mail: andrew.martin{at}health.wa.gov.au

Rationale: The majority of previous studies investigating asthma genetics have focused on cohorts with stable disease and have not defined mechanisms important during acute asthma. CD14 and CC16 each play a key role in biologically important inflammatory pathways and the gene of each has a functional promoter-region polymorphism.

Objectives: This study was designed to determine the influence of these polymorphisms on plasma levels of their products and clinical disease during acute asthma. We hypothesized that genotype-related differences in CD14 and CC16 production would be more marked during acute asthma and related to disease severity.

Methods: We studied 148 children on presentation with acute asthma and again in convalescence. CD14 C-159T and CC16 A38G genotypes were determined, and plasma levels of soluble CD14 (sCD14) and CC16 were measured at both times.

Measurements and Main Results: During acute asthma, plasma sCD14 levels were higher for the whole group (p = 0.003), but increases were only in subjects with CD14 –159TT (p = 0.003) and –159CT (p = 0.004), and not in those with –159CC. Plasma CC16 levels were also elevated acutely for the whole group (p = 0.013), but only in those with CC16 38GG (p = 0.043) and 38AG (p = 0.014), and not in those with CC16 38AA. Subjects with CD14 –159CC and CC16 38AA were more likely to have moderate or severe acute asthma.

Conclusions: Plasma levels of sCD14 and CC16 were higher during acute asthma in the subjects. Those with CD14 –159CC and CC16 38AA had no change in sCD14 and CC16 levels and more severe asthma.

Key Words: asthma • children • single nucleotide polymorphism

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