B579 - Interaction of FLG and SPINK5 polymorphisms in exczema in children - 09/11/2007

B number: 
Principal applicant name: 
Prof John Henderson (University of Bristol, UK)
Dr Alan Irvine (Not used 0, Not used 0), Dr Kate Northstone (University of Bristol, UK), Prof George Davey Smith (University of Bristol, UK), Prof W H Irwin McLean (University of Dundee, UK)
Title of project: 
Interaction of FLG and SPINK5 polymorphisms in exczema in children
Proposal summary: 

Filaggrin is a barrier protein in the skin. Two common variants of the filaggrin gene were reported by Palmer et al (Common loss-of-function variants of the epidermal barrier protein filaggrin are a major predisposing factor for atopic dermatitis. Nature Genetics 2006 Apr;38(4):441-6) to be strongly associated with eczema & these findings have been replicated by others, including us. SPINK5 (serine protease inhibitor Kazal-Type5) gene was discovered in association with Netherton Syndrome, a rare disorder that is ubiquitously associated with severe allergy.

Our collaborators have examined the associations of mutations in SPINK5 and FLG with eczema in a German population. The expected strong association between FLG and eczema was found. There appeared to be no strong evidence of a gene-only association of three mutations of SPINK5 and eczema in this cohort but there was evidence of a possible interaction between SPINK5 and FLG in association with eczema (see Appendix). We now wish to extend these observations by applying the same analyses to the data we have collected as part of our ongoing collaboration on FLG and allergis diseases.

The data are already available in a suitable form for analysis (Kate Northstone). THis proposal is to export these data (questionnaire and clinical assessments of eczema from birth to 13 years) to Dr Irvine & Mclean's German colaborators to carry out identical analytical methods to the attached. This will be more effieicient than analysing the data in-house. THe collaborators are willing to sign a confidentialiuty agreement and they will have access to a limited dataset (only that which is requred for this project under usual ALSPAC rules).

The genotyping costs of this project (FLG & SPINK5) have already been borne by the applicants. There are no additional resoucre issues for this project, which is part of an ongoing programme of analyses in collaboration with ALSPAC core personnel (JH, GDS, KN).

Date proposal received: 
Friday, 9 November, 2007
Date proposal approved: 
Friday, 9 November, 2007
Allergies, Respiratory, Atopy
Primary keyword: