Protocadherin-1 polymorphisms are associated with eczema in two Dutch birth cohorts

Authors

  • Henk Koning,

    1. Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, GRIAC research institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
    2. Laboratory of Allergology and Pulmonary Diseases, Department of Pathology and Medical Biology, GRIAC research institute, University Medical Center Groningen (UMCG), Groningen University, Groningen, The Netherlands
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  • Dirkje S. Postma,

    1. Pulmonology, GRIAC research institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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  • Bert Brunekreef,

    1. Epidemiology, Institute for Risk Assessment Sciences, University of Utrecht, Utrecht, The Netherlands
    2. Julius Center for Health Science and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
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  • Eric J. Duiverman,

    1. Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, GRIAC research institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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  • Henriette A. Smit,

    1. Julius Center for Health Science and Primary Care, University Medical Center Utrecht, Utrecht, The Netherlands
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  • Carel Thijs,

    1. Maastricht University, CAPHRI School of Public Health and Primary Care, and NUTRIM School of Nutrition, Toxicology and Metabolism, Department of Epidemiology, Maastricht, The Netherlands
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  • John Penders,

    1. Maastricht University, CAPHRI School of Public Health and Primary Care, and NUTRIM School of Nutrition, Toxicology and Metabolism, Department of Epidemiology, Maastricht, The Netherlands
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  • Marjan Kerkhof,

    1. Department of Epidemiology and Statistics, GRIAC research institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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  • Gerard H. Koppelman

    1. Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, GRIAC research institute, University Medical Center Groningen, University of Groningen, Groningen, The Netherlands
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Gerard H. Koppelman, Pediatric Pulmonology and Pediatric Allergology, Beatrix Children’s Hospital, University Medical Center Groningen, Groningen, PO Box 30.001, 9700 RB, Groningen, the Netherlands.
Tel.: +31 50 3614215
Fax: +31 50 3614235
E-mail: g.h.koppelman@bkk.umcg.nl

Abstract

To cite this article: Koning H, Postma DS, Brunekreef B, Duiverman EJ, Smit HA, Thijs C, Penders J, Kerkhof M, Koppelman GH. Protocadherin-1 polymorphisms are associated with eczema in two Dutch birth cohorts. Pediatr Allergy Immunol 2012: 23: 270–277.

Abstract

Background:  Eczema and asthma share a common genetic background and show linkage to chromosome 5q31-33. Protocadherin-1 (PCDH1) is located in this region and was identified as a susceptibility gene for bronchial hyper-responsiveness (BHR), a hallmark of asthma. PCDH1 encodes an adhesion molecule, expressed in airway and skin epithelium. We determined whether PCDH1 polymorphisms, previously associated with asthma or BHR, also associated with questionnaire and UK Working Party (UKWP) defined eczema.

Methods:  Four PCDH1 polymorphisms were genotyped in two Dutch birth cohorts, PIAMA (n = 967) and KOALA Birth Cohort Study (n = 1560). Association with eczema was determined by chi-square tests and generalized estimating equations (GEE).

Results:  Insertion deletion IVS3-116 was associated with development of UKWP eczema in PIAMA [age 4, OR = 1.90 (1.14–3.18)] and borderline with questionnaire-reported eczema in PIAMA [GEE, OR = 1.33 (0.98–1.81)]. Furthermore, IVS3-116 was associated with questionnaire-reported eczema in KOALA [age 1, OR = 1.44 (1.00–2.07)]. Pooled analysis of questionnaire-reported eczema of both cohorts resulted in a significant association of IVS3-116 with eczema [OR = 1.26 (1.01–1.58)]. Rs3822357 (A-allele) associated with protection for eczema in PIAMA only [questionnaires, OR = 0.19 (0.06–0.63)].

Conclusion: PCDH1 gene variant IVS3-116 associates with eczema in two independent birth cohorts. Combined with previous observations, this indicates a shared genetic susceptibility to BHR, asthma and eczema.

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