GENETICS OF LEFT VENTRICULAR HYPERTROPHY

High blood pressure makes the heart work harder and promotes enlargement of the left ventricle, left ventricular hypertrophy (LVH), which is an important risk factor for cardiovascular disease and death. LVH is characterized for the most part by two different sets of observable characteristics (genetic phenotypes): an enlarged left ventricle (1) due to increasing wall thickness and (2) due to increasing wall dilation. The molecular and pathological mechanisms by which either phenotype occurs is unknown. We do know, however, that both phenotypic variations of LVH are determined by quantitative and qualitive changes in the genetic expression of cardiac cells that result in structural alterations in the muscular tissue that affect the blood flow within the heart. Genetics, the study of heredity and the variation of inherited characteristics, therefore play a prominent role in the development of LVH. A genome-wide association (GWA) study to investigate the genetics of LVH and left ventricular mass index (LVMI) in a cross-sectional-study of 1,212 subjects of white European ancestry and 2.5 million nucleotide polymorphisms (SNPs) yielded a total of 19 genome-wide significant (P < 5x10-7) variants. The GWA revealed no genome-wide significant variants; however, at suggestive P value < 1x10-5 were found two potentially susceptible regions of 97.6 Kb in the SYT14 gene and 3.4 kb in the GAS1 gene for association with LVMI. Nineteen (19) susceptible regions harboring common variants associated with LVH and 2 potential regions associated with LVMI were found. Further functional genetic studies (relating to a variable quantity whose value depends on one or more other variables) are required to characterize the biological relevance of these findings to high blood pressure associated with enlargement of the left ventricle.