A common cortactin gene variation confers differential susceptibility to severe asthma

Shwu Fan Ma, Carlos Flores, Michael S. Wade, Steven M. Dudek, Dan L. Nicolae, Carole Ober, Joe GN Garcia

Research output: Contribution to journalArticle

12 Citations (Scopus)

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.

Original languageEnglish (US)
Pages (from-to)757-766
Number of pages10
JournalGenetic Epidemiology
Volume32
Issue number8
DOIs
StatePublished - 2008
Externally publishedYes

Fingerprint

Cortactin
Asthma
Genes
African Americans
Odds Ratio
Confidence Intervals
Myosin-Light-Chain Kinase
Microfilament Proteins
Disease Susceptibility
Case-Control Studies
Exons
Phenotype

Keywords

  • Asthma
  • CTTN
  • Cytoskeleton
  • MLCK
  • SNP

ASJC Scopus subject areas

  • Genetics(clinical)
  • Epidemiology

Cite this

A common cortactin gene variation confers differential susceptibility to severe asthma. / Ma, Shwu Fan; Flores, Carlos; Wade, Michael S.; Dudek, Steven M.; Nicolae, Dan L.; Ober, Carole; Garcia, Joe GN.

In: Genetic Epidemiology, Vol. 32, No. 8, 2008, p. 757-766.

Research output: Contribution to journalArticle

Ma, Shwu Fan ; Flores, Carlos ; Wade, Michael S. ; Dudek, Steven M. ; Nicolae, Dan L. ; Ober, Carole ; Garcia, Joe GN. / A common cortactin gene variation confers differential susceptibility to severe asthma. In: Genetic Epidemiology. 2008 ; Vol. 32, No. 8. pp. 757-766.
@article{4ba61978fd094296ad9537a17d1a42a2,
title = "A common cortactin gene variation confers differential susceptibility to severe asthma",
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.",
keywords = "Asthma, CTTN, Cytoskeleton, MLCK, SNP",
author = "Ma, {Shwu Fan} and Carlos Flores and Wade, {Michael S.} and Dudek, {Steven M.} and Nicolae, {Dan L.} and Carole Ober and Garcia, {Joe GN}",
year = "2008",
doi = "10.1002/gepi.20343",
language = "English (US)",
volume = "32",
pages = "757--766",
journal = "Genetic Epidemiology",
issn = "0741-0395",
publisher = "Wiley-Liss Inc.",
number = "8",

}

TY - JOUR

T1 - A common cortactin gene variation confers differential susceptibility to severe asthma

AU - Ma, Shwu Fan

AU - Flores, Carlos

AU - Wade, Michael S.

AU - Dudek, Steven M.

AU - Nicolae, Dan L.

AU - Ober, Carole

AU - Garcia, Joe GN

PY - 2008

Y1 - 2008

N2 - 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.

AB - 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.

KW - Asthma

KW - CTTN

KW - Cytoskeleton

KW - MLCK

KW - SNP

UR - http://www.scopus.com/inward/record.url?scp=58949100173&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=58949100173&partnerID=8YFLogxK

U2 - 10.1002/gepi.20343

DO - 10.1002/gepi.20343

M3 - Article

VL - 32

SP - 757

EP - 766

JO - Genetic Epidemiology

JF - Genetic Epidemiology

SN - 0741-0395

IS - 8

ER -