Wiener klinische Wochenschrift

, Volume 122, Issue 19–20, pp 551–557 | Cite as

Lower prevalence of common filaggrin mutations in a community sample of atopic eczema: is disease severity important?

  • Robert Gruber
  • Andreas R. Janecke
  • Daniela Grabher
  • Elisabeth Horak
  • Matthias Schmuth
  • Peter Lercher
Original article

Summary

BACKGROUND: Recent studies have shown an association of loss-of-function mutations in the filaggrin gene (FLG) with ichthyosis vulgaris and atopic eczema (AE). Case selection may have distorted the hitherto reported prevalence of FLG mutations and their relation to atopic disease. The aim of the study was to determine the true population prevalence of FLG mutations in unselected children with and without reported physician diagnoses of asthma, allergic rhinitis and AE and their relationship with family history of atopic disease. METHODS: We used a nested case-control design by sampling children with reported doctor's diagnoses of AE, asthma and allergic rhinitis and randomly selected controls from a larger cross-sectional study (n = 1263). Most common FLG mutations R501X, 2282del4, and R2447X were screened in DNA extracted from defrosted urine samples. The relationship of the combined FLG variants with atopic diseases and with reported family history of AE, asthma, and rhinitis was assessed. RESULTS: In the patient group one homozygote (R501X/R501X), 4 compound heterozygotes (3 R501X/2282del4, one 2282del4/R2447X), and 17 heterozygotes (10 R501X/wt, 5 2282del4/wt, and 2 R2447X/wt), in the control group 9 heterozygotes (5 R501X/wt, 4 2282del4/wt) were detected. The combined prevalence of FLG loss-of-function alleles was 5% in the control group and 9% in the atopic sample. In a subgroup analysis, the combination of allergic rhinitis and AE showed a significant relationship with FLG mutations, OR = 3.7 (1.01–12.67, p = 0.024). Likewise, significant relations with reported family history of asthma, OR = 4.35 (1.78–10.62, p = 0.0012), allergic rhinitis, OR = 2.33 (1.49–3.63, p = 0.0002), and AE, OR = 5.08 (2.78–9.30, p ≤ 0.0001) were observed. In contrast to clinical studies with higher percentages of severely affected persons, FLG mutations here showed a moderate association with atopic disease. CONCLUSIONS: Case selection may be responsible for overestimating the prevalence of FLG mutations in atopic disease.

Keywords

Allergic rhinitis Asthma Atopic eczema Filaggrin Public health Allergische Rhinitis Asthma bronchiale Neurodermitis Filaggrin Gesundheitswesen 

Abbreviations

AE

Atopic eczema

CAMP

Childhood Asthma Management Program

CI

Confidence interval

DNA

Desoxyribonucleic acid

FeNO

Fractional exhaled nitric oxide

FEV1

Forced expiratory volume in one second

FLG

Filaggrin

FVC

Forced vital capacity

ISAAC

International Study of Asthma and Allergies in Childhood

MAS

Multicenter Allergy Study

MEF50

Forced expiratory flow at 50% of FVC

OR

Odds ratio

PCR

Polymerase chain reaction

SCORAD

Scoring Atopic Dermatitis system

Geringere Prävalenz häufiger Filaggrin-Mutationen in einer unselektionierten Neurodermitis-Kohorte: Ist der Schweregrad der Erkrankung bedeutend?

Zusammenfassung

HINTERGRUND: In kürzlich publizierten Studien konnte ein Zusammenhang zwischen Funktionsverlust-Mutationen im Filaggringen (FLG) mit Ichthyosis vulgaris und Neurodermitis (AE) gezeigt werden. Die bisher berichteten Prävalenzen von FLG Mutationen und deren Relation zu atopischen Erkrankungen könnte jedoch durch Fall Selektion verzerrt werden. Daher war es Ziel dieser Studie, die wahre Populations-Prävalenz der FLG Mutationen in unselektionierten Kindern mit und ohne ärztliche Diagnose von Asthma bronchiale, allergischer Rhinitis und Neurodermitis sowie den familiären atopischen Hintergrund zu bestimmen. METHODEN: Verwendet wurde ein verschachteltes Case-control Design, bei dem Kinder mit ärztlicher Diagnose von Asthma bronchiale, allergischer Rhinitis und Neurodermitis sowie wahllos selektionierte Kontrollen aus einer größeren Querschnittsstudie (n = 1263) inkludiert wurden. Es wurde auf die häufigsten in Europa vorkommenden FLG Mutationen R501X, 2282del4 und R2447X gescreent, die DNA hierfür wurde aus aufgetauten Urinproben extrahiert. Das Verhältnis der kombinierten FLG Varianten mit atopischen Erkrankungen und mit berichteter Familienanamnese von Asthma bronchiale, allergischer Rhinitis und Neurodermitis wurde bestimmt. ERGEBNISSE: In der Patientengruppe fanden sich ein homozygoter (R501X/R501X), 4 compound heterozygote (3 R501X/2282del4, ein 2282del4/R2447X) und 17 heterozygote (10 R501X/wt, 5 2282del4/wt, 2 R2447X/wt), in der Kontrollgruppe 9 heterozygote (5 R501X/wt, 4 2282del4/wt) Individuen. Die kombinierte Prävalenz von FLG Funktionsverlust-Mutationen betrug 5 % in der Kontroll- und 9 % in der Atopie-Gruppe. In einer Subtypenanalyse zeigte die Kombination von allergischer Rhinitis und Neurodermitis eine signifikante Assoziation mit FLG Mutationen, OR = 3,7 (1,01–12,67; p = 0,024). Ebenso wurden signifikante Zusammenhänge mit berichteter Familienanamnese von Asthma bronchiale, OR = 4,35 (1,78–10,62; p = 0,0012), allergischer Rhinitis, OR = 2,33 (1,49–3,63; p = 0,0002) und Neurodermitis, OR = 5,08 (2,78–9,30; p ≤ 0,0001) gefunden. Im Gegensatz zu klinischen Studien mit prozentuell mehr schwer betroffenen Personen, zeigten FLG Mutationen in der vorliegenden Arbeit eine lediglich moderate Assoziation mit atopischen Erkrankungen. SCHLUSSFOLGERUNG: Fall Selektion könnte zu einer Überschätzung der Prävalenz von FLG Mutationen in atopischen Erkrankungen führen.

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Copyright information

© Springer-Verlag 2010

Authors and Affiliations

  • Robert Gruber
    • 1
    • 2
  • Andreas R. Janecke
    • 2
  • Daniela Grabher
    • 1
    • 2
  • Elisabeth Horak
    • 3
  • Matthias Schmuth
    • 1
  • Peter Lercher
    • 4
  1. 1.Department of DermatologyInnsbruck Medical UniversityInnsbruckAustria
  2. 2.Department of Medical Genetics, Molecular and Clinical PharmacologyInnsbruck Medical UniversityInnsbruckAustria
  3. 3.Department of Paediatrics and AdolescentsInnsbruck Medical UniversityInnsbruckAustria
  4. 4.Section for Social MedicineInnsbruck Medical UniversityInnsbruckAustria

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