Protocadherin-1 polymorphisms are associated with eczema in two Dutch birth cohorts
Article first published online: 19 SEP 2011
© 2011 John Wiley & Sons A/S
Pediatric Allergy and Immunology
Volume 23, Issue 3, pages 270–277, May 2012
How to Cite
Koning, H., Postma, D. S., Brunekreef, B., Duiverman, E. J., Smit, H. A., Thijs, C., Penders, J., Kerkhof, M. and Koppelman, G. H. (2012), Protocadherin-1 polymorphisms are associated with eczema in two Dutch birth cohorts. Pediatric Allergy and Immunology, 23: 270–277. doi: 10.1111/j.1399-3038.2011.01201.x
- Issue published online: 17 APR 2012
- Article first published online: 19 SEP 2011
- Accepted for publication 7 July 2011
- birth cohort;
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.
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.