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A follow-up study for left ventricular mass on chromosome 12p11 identifies potential candidate genes

David Della-Morte15, Ashley Beecham2, Tatjana Rundek1, Liyong Wang2, Mark S McClendon1, Susan Slifer2, Susan H Blanton2, Marco R Di Tullio4 and Ralph L Sacco123*

Author Affiliations

1 Department of Neurology, Evelyn F. McKnight Brain Institute, Miller School of Medicine, University of Miami, Miami, FL, USA

2 Department of Human Genetics, Hussman Institute for Human Genomics, Miller School of Medicine, University of Miami, Miami, FL, USA

3 Department of Public Health and Epidemiology, Miller School of Medicine, University of Miami, Miami, FL, USA

4 Department of Medicine, Columbia University, New York, NY, USA

5 Department of Laboratory Medicine & Advanced Biotechnologies, IRCCS San Raffaele Pisana, Rome, Italy

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BMC Medical Genetics 2011, 12:100  doi:10.1186/1471-2350-12-100

Published: 26 July 2011



Left ventricular mass (LVM) is an important risk factor for cardiovascular disease. Previously we found evidence for linkage to chromosome 12p11 in Dominican families, with a significant increase in a subset of families with high average waist circumference (WC). In the present study, we use association analysis to further study the genetic effect on LVM.


Association analysis with LVM was done in the one LOD critical region of the linkage peak in an independent sample of 897 Caribbean Hispanics. Genotype data were available on 7085 SNPs from 23 to 53 MB on chromosome 12p11. Adjustment was made for vascular risk factors and population substructure using an additive genetic model. Subset analysis by WC was performed to test for a difference in genetic effects between the high and low WC subsets.


In the overall analysis, the most significant association was found to rs10743465, downstream of the SOX5 gene (p = 1.27E-05). Also, 19 additional SNPs had nominal p < 0.001. In the subset analysis, the most significant difference in genetic effect between those with high and low WC occurred with rs1157480 (p = 1.37E-04 for the difference in β coefficients), located upstream of TMTC1. Twelve additional SNPs in or near 6 genes had p < 0.001.


The current study supports previously identified evidence by linkage for a genetic effect on LVM on chromosome 12p11 using association analysis in population-based Caribbean Hispanic cohort. SOX5 may play an important role in the regulation of LVM. An interaction of TMTC1 with abdominal obesity may contribute to phenotypic variation of LVM.