TY - JOUR
T1 - Uncommon Filaggrin Variants Are Associated with Persistent Atopic Dermatitis in African Americans
AU - Margolis, David J.
AU - Mitra, Nandita
AU - Gochnauer, Heather
AU - Wubbenhorst, Bradley
AU - D'Andrea, Kurt
AU - Kraya, Adam
AU - Hoffstad, Ole
AU - Gupta, Jayanta
AU - Kim, Brian
AU - Yan, Albert
AU - Fuxench, Zelma Chiesa
AU - Nathanson, Katherine L.
N1 - Funding Information:
This study was funded by support from the National Institutes of Health National Institute of Arthritis and Musculoskeletal and Skin Diseases (R01-AR069062). The sponsor did not have a role in the design of the study; the collection, analysis, or interpretation of the data; the preparation of this report; or the decision to submit this report for publication.
Publisher Copyright:
© 2018 The Authors
PY - 2018/7
Y1 - 2018/7
N2 - Atopic dermatitis (AD) is a common illness that has been associated with filaggrin gene (FLG) loss of function (LoF) variation. In African Americans, a group that commonly has AD and has not been well studied, FLG LoF variation is rarely found. Our objective was to use massively parallel sequencing to evaluate FLG LoF variation in children of African ancestry to evaluate the association between FLG LoF variation and AD and AD persistence. We studied 262 African American children with AD. Nine unique FLG exon 3 LoF variants were identified for an overall minor variant frequency of 6.30% (95% confidence interval [CI] = 4.37–8.73). The most common variants were p.R501X (1.72%, 95% CI = 0.79–3.24), p.S3316X (1.34%, 95% CI = 0.54–2.73), and p.R826X (0.95%, 95% CI = 0.31–2.2). Over an average follow-up period of 96.4 (95% CI = 92.0–100.8) months, African American children with FLG LoF were less likely to be symptom free (odds ratio = 0.36, 95% CI = 0.14–0.89, P = 0.027) compared with a FLG wild-type child. In contrast to previous reports, uncommon FLG LoF variants in African American children exist and are associated with AD and more persistent AD. In contrast to Europeans, no FLG LoF variants predominate in African American children. Properly determining FLG LoF status requires advanced sequencing techniques.
AB - Atopic dermatitis (AD) is a common illness that has been associated with filaggrin gene (FLG) loss of function (LoF) variation. In African Americans, a group that commonly has AD and has not been well studied, FLG LoF variation is rarely found. Our objective was to use massively parallel sequencing to evaluate FLG LoF variation in children of African ancestry to evaluate the association between FLG LoF variation and AD and AD persistence. We studied 262 African American children with AD. Nine unique FLG exon 3 LoF variants were identified for an overall minor variant frequency of 6.30% (95% confidence interval [CI] = 4.37–8.73). The most common variants were p.R501X (1.72%, 95% CI = 0.79–3.24), p.S3316X (1.34%, 95% CI = 0.54–2.73), and p.R826X (0.95%, 95% CI = 0.31–2.2). Over an average follow-up period of 96.4 (95% CI = 92.0–100.8) months, African American children with FLG LoF were less likely to be symptom free (odds ratio = 0.36, 95% CI = 0.14–0.89, P = 0.027) compared with a FLG wild-type child. In contrast to previous reports, uncommon FLG LoF variants in African American children exist and are associated with AD and more persistent AD. In contrast to Europeans, no FLG LoF variants predominate in African American children. Properly determining FLG LoF status requires advanced sequencing techniques.
UR - http://www.scopus.com/inward/record.url?scp=85044140433&partnerID=8YFLogxK
U2 - 10.1016/j.jid.2018.01.029
DO - 10.1016/j.jid.2018.01.029
M3 - Article
C2 - 29428354
AN - SCOPUS:85044140433
VL - 138
SP - 1501
EP - 1506
JO - Journal of Investigative Dermatology
JF - Journal of Investigative Dermatology
SN - 0022-202X
IS - 7
ER -