Premium
Common Susceptibility Variants Examined for Association with Dilated Cardiomyopathy
Author(s) -
Rampersaud Evadnie,
Kinnamon Daniel D.,
Hamilton Kara,
Khuri Sawsan,
Hershberger Ray E.,
Martin Eden R.
Publication year - 2010
Publication title -
annals of human genetics
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.537
H-Index - 77
eISSN - 1469-1809
pISSN - 0003-4800
DOI - 10.1111/j.1469-1809.2010.00566.x
Subject(s) - myh7 , dilated cardiomyopathy , genetics , biology , proband , candidate gene , gene , mutation , medicine , heart failure , gene isoform
Summary Rare mutations in more than 20 genes have been suggested to cause dilated cardiomyopathy (DCM), but explain only a small percentage of cases, mainly in familial forms. We hypothesised that more common variants may also play a role in increasing genetic susceptibility to DCM, similar to that observed in other common complex disorders. To test this hypothesis, we performed case‐control analyses on all DNA polymorphic variation identified in a resequencing study of six candidate DCM genes ( CSRP3 , LDB3 , MYH7, SCN5A , TCAP , and TNNT2 ) conducted in 289 unrelated white probands with DCM of unknown cause and 188 unrelated white controls. In univariate analyses, we identified associated common variants at LDB3 site 10779, LDB3 site 57877, MYH7 sites 16384 and 17404, and TCAP sites 140 and 1735. Multivariate analyses to examine the joint effects of multiple gene variants confirmed univariate results for MYH7 and TCAP and identified a block of nine variants in MYH7 that was strongly associated with DCM. Common variants in genes known to be causative of DCM may play a role in genetic susceptibility to DCM. Our results suggest that examination of common genetic variants may be warranted in future studies of DCM and other Mendelian‐like disorders.