Volume 6 Supplement 3

Fifth Annual Research Conference: Innovation from Cell to Society

Open Access

Association between filaggrin family member genes, asthma, atopy and atopic asthma with atopic dermatitis history in the subjects from the Saguenay-Lac-Saint-Jean founder population

  • Marie-Hélène Lambert1, 2,
  • Karine Tremblay3,
  • Anne-Marie Madore1, 2 and
  • Catherine Laprise1
Allergy, Asthma & Clinical Immunology20106(Suppl 3):P4

https://doi.org/10.1186/1710-1492-6-S3-P4

Published: 26 November 2010

Objective/purpose

To perform an association study between the filaggrin (FLG) and the filaggrin family member 2 (FLG2) tagging single nucleotide polymorphisms (tagSNPs) and asthma, atopy, atopic asthma, as well as these affections in the presence of atopic dermatitis (AD).

Methods

Five tagSNPs covering FLG have been genotyped in 237 trios from the Saguenay-Lac-Saint-Jean population using a Sequenom panel. In addition, a genome-wide association study (GWAS) has also been done for the same trios in the large-scale GABRIEL project http://www.gabriel-fp6.org/. The polymorphisms (SNPs) included in FLG and FLG2 as well as those in the 3' and 5' UTR regions were extracted. Six SNPs were extracted for FLG (for a total of 11 SNPs when including the Sequenom panel) and 2 SNPs for FLG2. The association study for all the affections was done using a family-based association test (FBAT). The results were corrected using the Li and Ji method [1].

Findings

Positive associations were found between a haplotype block formed by FLG rs2184951 and rs12730241 (H1) and asthma and related phenotypes (see results in Table 1).
Table 1

Association of FLG haplotype and tagSNPs with asthma and atopy (A) and with asthma and atopy that co-occur with the presence of a personal history of atopic dermatitis (B)

A

SNP

Allele

Asthma

Atopy

Atopic asthma

  

S:E(S)

Z

p

S:E(S)

Z

p

S:E(S)

Z

p

rs3126085

A

32.0:50.2

-3.48

0.0005

35.0:49.8

-2.94

0.0033

25.0:37.2

-2.74

0.0061

 

G

148.0:129.8

3.48

 

141.0:126.2

2.94

 

109.0:96.8

2.74

 

B

SNP/Haplotype

Allele

Asthma and AD

Atopy and AD

Atopic asthma and AD

  

S:E(S)

Z

p

S:E(S)

Z

P

S:E(S)

Z

p

rs3126085

A

14.0:24.0

-2.94

0.0033

16.0:24.5

-2.59

0.0097

10.0:18.0

-2.74

0.0062

 

G

66.0:56.0

2.94

 

62.0:53.5

2.59

 

52.0:44.0

2.74

 

H1

T G

75.0:66.0

2.61

0.009

75.0:64.0

3.33

0.0009

60.0:51.0

2.94

0.0033

Positives associations were also found between FLG2 rs2065954 and rs3818831 and asthma (p = 0.0033 and p = 0.0016), atopy (p = 0.00009 and p = 0.00006) and atopic asthma (p = 0.0004 and p = 0.0002) in all cases in the presence of AD as well as AD alone (p = 0.0016 and p = 0.0007 respectively).

Deliverables

To conclude, FLG and FLG2 are genes associated with asthma. Functional studies will be necessary to document the molecular structure (sequence) and role of these genes in asthma and the impact of the genetic variants.

Relevance

Identification of associated genes is fundamental to document the molecular nature of asthma in order to increase knowledge of the pathophysiology of this complex trait.

Authors’ Affiliations

(1)
Université du Québec à Chicoutimi
(2)
Université Laval
(3)
Université de Montréal

References

  1. Li J, Ji L: Adjusting multiple testing in multilocus analyses using the eigenvalues of a correlation matrix. Heredity. 2005, 95: 221-227. 10.1038/sj.hdy.6800717.PubMedView ArticleGoogle Scholar

Copyright

© Lambert et al; licensee BioMed Central Ltd. 2010

This article is published under license to BioMed Central Ltd.

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