Abstract
BackgroundEpidemiological studies have shown considerable heritability of blood pressure, thus suggesting a role for genetic factors. Previous studies have shown an association of a single nucleotide polymorphism rs5068 in the NPPA locus gene with higher levels of circulating atrial natriuretic peptide as well as with lower intra individual blood pressure, but up to date, no association between rs5068 and cardiac organ damage, i.e. left ventricular hypertrophy, has been accounted for in humans. We sought to explore if rs5068 is associated with left ventricular hypertrophy as measured by echocardiographic examination in a non-diabetic population.Methods968 non-diabetic individuals from the Malmö Preventive Project (mean age 67 years; 31% women) were genotyped and examined with echocardiography. Logistic regression was used to adjust for covariates.ResultsThe minor allele of rs5068 was associated with decreased prevalence of left ventricular hypertrophy (p = 0.021) after adjustment for sex and age. In the multivariate logistic analysis including; age, sex, systolic blood pressure, antihypertensive and/or cardioprotective treatment, body mass index and fasting plasma glucose, the association of rs5068 with left ventricular hypertrophy was, as expected, attenuated (p = 0.061).ConclusionIn a non-diabetic population, the minor allele of rs5068 was associated with lower left ventricular mass. These findings suggest that rs5068, or genetic variants in linkage disequilibrium, might affect susceptibility to left ventricular hypertrophy and support the possible protective role of natriuretic peptides.
Highlights
Epidemiological studies have shown considerable heritability of blood pressure, suggesting a role for genetic factors
Animal studies have shown that over expression of natriuretic peptide genes is associated with low blood pressure (BP), whereas under expression is associated with high BP and left ventricular hypertrophy (LVH) [4,5], and studies on
Associations between common variations in natriuretic peptide precursor A (NPPA)-natriuretic peptide precursor B (NPPB) locus genes and higher levels of circulating Atrial natriuretic peptide (ANP) were found in a recent study as well as association with lower interindividual BP, with the strongest effect for rs5068 [12], findings that have been replicated in larger cohorts [13]
Summary
Epidemiological studies have shown considerable heritability of blood pressure, suggesting a role for genetic factors. Previous studies have shown an association of a single nucleotide polymorphism rs5068 in the NPPA locus gene with higher levels of circulating atrial natriuretic peptide as well as with lower intra individual blood pressure, but up to date, no association between rs5068 and cardiac organ damage, i.e. left ventricular hypertrophy, has been accounted for in humans. We sought to explore if rs5068 is associated with left ventricular hypertrophy as measured by echocardiographic examination in a non-diabetic population. The minor allele of rs5068 has been associated with favorable cardiometabolic profile [14], and there is evidence for an important protective role of the natriuretic peptides in individuals with coronary artery disease [15], but surprisingly no association with echocardiographic evidence of cardiac organ damage, such as LVH, for this particular SNP. Since LVH is well known to be overrepresented in patients with diabetes mellitus [11,16,17,18,19] the inclusion of subjects with diabetes, 17% and 15% respectively) might explain the lack of association of rs5068 and LVH [14,15].
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