Abstract P528: Modifiable Factors Affecting BP in Identical Twins

Abstract

Background: Genetic factors determining blood pressure (BP) are largely unmodifiable. Understanding the effects of physiologic, environmental, and epigenetic (modifiable) factors on BP levels can improve strategies for hypertension (HTN) control. Monozygotic (MZ) twins with identical genetic background are a good model to study the effect of these factors on BP. Methods: Seventy pairs of MZ twins were from Milwaukee, WI and Michigan State University Twin Registry, East Lansing, MI (62% women; age of 44 ± 10 years). BPs (measured in triplicate and averaged), anthropometrics, physical activity (Rapid Assessment of Physical Activity), and sodium intake measurements (Block Sodium Screener) were obtained. DNA was obtained from T-lymphocytes for methylation (epigenetic) sequencing analysis. Differences in systolic (SBP) and diastolic (DBP) BPs between co-twins were used as continuous variables for these analyses. Results: Mean SBP was 124 ± 15 mm Hg (mean ± SD) and DBP was 78 ± 11 mm Hg. Average differences in SBP and DBP among co-twins were 8 ± 9 and 7 ± 6 mm Hg respectively. Twin pairs were considered concordant or discordant based on BP difference of 10 mm Hg between co-twins or one twin being hypertensive. Discordant twins as a group had higher BMI and waist circumference (WC) compared to concordant twins (p<0.05). Among discordant twins, the co-twin with higher BPs tended to have higher waist circumference (WC) (105 ± 15 vs. 98 ± 18 cm) and dietary salt intake (3900 ± 1437 vs. 3261 ± 1058 mg/d) even though they did not reach statistical significance. There were no differences in physical activity or education levels. Genome-wide methylation analyses revealed that 3 loci were associated with SBP difference and 2 were associated with DBP difference at an unadjusted significance level of p < 10 -4 . Two sites reached an adjusted significance level of 0.08 with SBP difference. Conclusions: In this study, we identified several differentially methylated sites of interest in relation to BP among MZ twins. In addition, higher central adiposity and sodium intake may contribute to BP levels among MZ twins. Understanding the relationship of modifiable risk factors such as WC and sodium intake with methylation changes may shed light into novel pathogenic pathways for HTN.