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

Abstract

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.