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Τετάρτη 22 Νοεμβρίου 2017

The COL5A3 and MMP9 genes interact in eczema susceptibility

Abstract

Background

Genetic studies of eczema have identified many genes, which explain only 14% of the heritability. Missing heritability may be partly due to ignored Gene–Gene (G-G) interactions.

Objective

Our aim was to detect new interacting genes involved in eczema.

Methods

The search for G-G interaction in eczema was conducted using a two-step approach, which included as a first step, a biological selection of genes, which are involved either in the skin or epidermis development or in the collagen metabolism, and as a second-step, an interaction analysis of the selected genes. Analyses were carried out at both SNP and gene levels in three asthma-ascertained family samples: the discovery dataset of 388 EGEA (Epidemiological study on the Genetics and Environment of Asthma) families and the two replication datasets of 253 SLSJ (Saguenay-Lac-Saint-Jean) families and 207 MRCA (Medical Research Council) families.

Results

One pair of SNPs, rs2287807 in COL5A3 and rs17576 in MMP9, that were detected in EGEA at P ≤ 10-5 showed significant interaction by meta-analysis of EGEA, SLSJ and MRCA samples (P=1.1x10-8 under the significant threshold of 10-7). Gene-based analysis confirmed strong interaction between COL5A3 and MMP9 (P=4x10-8 under the significant threshold of 4x10-6) by meta-analysis of the three datasets. When stratifying the data on asthma, this interaction remained in both groups of asthmatic and non-asthmatic subjects.

Conclusion

This study identified significant interaction between two new genes, COL5A3 and MMP9, which may be accounted for by a degradation of COL5A3 by MMP9 influencing eczema susceptibility.

Further confirmation of this interaction as well as functional studies are needed to better understand the role of these genes in eczema.

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