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

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.Increase in left ventricle mass (LVM) is considered a compensatory process which maintains cardiac function in response to noxious stimuli, such as hypertension, obesity and heart damage [1]. Increase in LVM is one of the most important cardiac risk factors for stroke and cardiovascular disease (CVD), including myocardial infarction (MI), and chronic heart failure (HF), independent of age, sex and race-ethnicity [2]. Previously in the Northern Manhattan Study (NOMAS), we demonstrated that LVM was significantly associated with risk of stroke, especially in Caribbean Hispanic individuals [3].Hypertension, obesity, and diabetes are the most important determinants for hypertrophy of the left ventricle (LVH) [4]. Many genes related to these and other vascular ris