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

<p>Abstract</p> <p>Background</p> <p>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.</p> <p>Methods</p> <p>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.</p> <p>Results</p> <p>In the overall analysis, the most significant association was found to rs10743465, downstream of the <it>SOX5 </it>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 <it>TMTC1</it>. Twelve additional SNPs in or near 6 genes had p < 0.001.</p> <p>Conclusions</p> <p>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. <it>SOX5 </it>may play an important role in the regulation of LVM. An interaction of <it>TMTC1 </it>with abdominal obesity may contribute to phenotypic variation of LVM.</p

Distinct QTLs are linked to cardiac left ventricular mass in a sex-specific manner in a normotensive inbred rat intercross

Genetic mapping of the progeny of an F2 intercross between WKY and WKHA rats had previously allowed us to detect male-specific linkage between locus Cm24 and left ventricular mass index (LVMI). By further expanding that analysis, we detected additional loci that were all linked to LVMI in a sexspecific manner despite their autosomal location. In males, we detected one additional locus (Lvm8) on Chromosome 5 (LOD = 3.4), the two loci Lvm13 (LOD = 4.5) and Lvm9 (LOD = 2.8) on Chromosome 17, and locus Lvm10 (LOD = 4.2) on Chromosome 12. The locus Lvm13 had the same boundaries as locus Cm26 previously reported by others using a different cross. None of these loci showed linkage to LVM in females. In contrast, we identified in females the novel locus Lvm11 on Chromosome 15 (LOD = 2.8) and locus Lvm12 (LOD = 2.7) that had the same boundaries on Chromosome 3 as locus Cm25 detected previously by others using a cross of other normotensive strains. In prepubertal males, there were no differences in the width of cardiomyocytes from WKY and WKHA rats, but cardiomyocytes from WKHA became progressively wider than that of WKY as sexual maturation progressed. Altogether, these results provide evidence that distinct genes may influence LVMI of rats in a sexdependent manner, maybe by involving sex-specific interactions of sex steroids with particular genes involved in the determination of LVMI and/or cardiomyocyte width.Bastien Llamas, Zhibin Jiang, Marie-Line Rainville, Sylvie Picard and Christian F. Descheppe