Atopy history and the genomics of wheezing after influenza vaccination in children 6-59 months of age |
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Authors: | Miller E Kathryn Dumitrescu Logan Cupp Chelsea Dorris Stacy Taylor Sallee Sparks Robert Fawkes Diane Frontiero Virginia Rezendes Anne M Marchant Colin Edwards Kathryn M Crawford Dana C |
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Affiliation: | a Department of Pediatrics, Vanderbilt University Medical Center, CCC-5323 Medical Center North, Nashville, TN 37232, USA b Center for Human Genetics Research, Vanderbilt University Medical Center, 519 Light Hall, 2215 Garland Avenue, Nashville, TN 37232, USA c Department of Molecular Physiology and Biophysics, Vanderbilt University Medical Center, 1211 Medical Center Drive, Nashville, TN, 37232, USA d Boston University Medical Center, 670 Albany Street, 6th Floor, Suite 601, Boston, MA 02118, USA |
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Abstract: | BackgroundA multinational clinical trial compared the safety and efficacy of intranasal trivalent live attenuated influenza vaccine (LAIV) with intramuscular trivalent inactivated vaccine (TIV) in very young children prior to the 2004-5 influenza season [1]. Wheezing was noted more often in recipients of LAIV and laboratory-confirmed influenza infection was noted more often in recipients of TIV. We sought to determine whether epidemiologic or genetic factors were associated with these outcomes.MethodsAtopy surveys and DNA collections were performed in trial participants at two United States sites, Nashville, TN and Boston, MA. DNA samples were genotyped on Illumina Infinium 610 or 660-Quad. Standard allelic tests of association were performed.ResultsAt the Nashville and Boston sites, a total of 99 children completed the trial, 6 (1 TIV, 5 LAIV) developed medically attended wheezing within 42 days following vaccination, and 8 (5 TIV, 3 LAIV) developed laboratory-confirmed influenza during the season. Eighty-one surveys and 70 DNA samples were collected. Family history of asthma (p = 0.001) was associated with wheezing after vaccination. Of 468,458 single nucleotide polymorphisms tested in the genome-wide association study (GWAS), none achieved genome-wide significance for either wheezing after vaccination or laboratory-confirmed influenza infection.ConclusionsFamily history of asthma appears to be a risk factor for wheezing after influenza vaccination. Given the limitations of the sample size, our pilot study demonstrated the feasibility of performing a GWAS but was not able to determine genetic polymorphisms associated with wheezing after influenza immunization. |
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Keywords: | LAIV, intranasal trivalent live attenuated influenza vaccine TIV, trivalent inactivated vaccine GWAS, genome-wide association study AEs, adverse events ISAAC, International Study of Asthma and Allergies in Childhood |
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