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. 2008 Dec;32(8):757-66.
doi: 10.1002/gepi.20343.

A common cortactin gene variation confers differential susceptibility to severe asthma

Shwu-Fan Ma  1 , Carlos Flores, Michael S Wade, Steven M Dudek, Dan L Nicolae, Carole Ober, Joe G N Garcia
Affiliations

A common cortactin gene variation confers differential susceptibility to severe asthma

Shwu-Fan Ma et al. Genet Epidemiol. 2008 Dec.

Abstract

Genomic regions with replicated linkage to asthma-related phenotypes likely harbor multiple susceptibility loci with relatively minor effects on disease susceptibility. The 11q13 chromosomal region has repeatedly been linked to asthma with five genes residing in this region with reported replicated associations. Cortactin, an actin-binding protein encoded by the CTTN gene in 11q13, constitutes a key regulator of cytoskeletal dynamics and contractile cell machinery, events facilitated by interaction with myosin light chain kinase; encoded by MYLK, a gene we recently reported as associated with severe asthma in African Americans. To evaluate potential association of CTTN gene variation with asthma susceptibility, CTTN exons and flanking regions were re-sequenced in 48 non-asthmatic multiethnic samples, leading to selection of nine tagging polymorphisms for case-control association studies in individuals of European and African descent. After ancestry adjustments, an intronic variant (rs3802780) was significantly associated with severe asthma (odds ratio [OR]: 1.71; 95% confidence interval [CI]: 1.20-2.43; p=0.003) in a joint analysis. Further analyses evidenced independent and additive effects of CTTN and MYLK risk variants for severe asthma susceptibility in African Americans (accumulated OR: 2.93, 95% CI: 1.40-6.13, p=0.004). These data suggest that CTTN gene variation may contribute to severe asthma and that the combined effects of CTTN and MYLK risk polymorphisms may further increase susceptibility to severe asthma in African Americans harboring both genetic variants.

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Figures

Figure 1
Figure 1
Linkage disequilibrium patterns (measured by r2) in African (upper panel) and European Americans (lower panel). Boxes denote the approximate location of CTTN gene exons. Polymorphisms are numbered as in Table I.
Figure 2
Figure 2
Combined effects of CTTN (rs3802780) and MYLK (rs9840993) genotypes in severe asthma in African Americans. Histograms indicating the odds ratios for the different genotype combinations for the CTTN rs3802780 G/A and MYLK rs9840993 T/C compared to the reference non risk genotypes for both SNPs. Genotype counts in cases (above the diagonal) and controls (below the diagonal) are also shown.
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