Abstract P264: DNA Methylation and Differences in Blood Pressure Levels in Monozygotic Twins

Abstract

Background: The development of common forms of hypertension (HTN) involves both genetic and environmental factors. Methylation changes (one of the epigenetic modifications) of DNA may play a role in the regulation of BP and development of HTN, and may result from interaction of specific genes with the environment. The current study investigates the relationship between genome-wide changes in DNA methylation in T-lymphocytes and BP level differences among monozygotic twins, who have identical DNA sequences. Methods: In a preliminary study, we recruited 24 pairs of monozygotic twins (60% women) with a mean age of 44 ± 10 years. Zygosity was determined via self-report or participants’ responses to a standard zygosity questionnaire. BPs were measured in triplicate after 5 minutes of rest at one minute intervals and averaged. Anthropometrics measurements were obtained along with blood for isolation of T-lymphocytes. DNA from T-lymphocytes was used to perform reduced representation bisulfite sequencing (RRBS) to measure methylation levels at single-base resolution in these subjects. Average differences in systolic (SBP) and diastolic (DBP) BPs were used as continuous variables for these analyses. Results: Mean SBP was 124 ± 15 (range (r): 97-174) mm Hg and mean DBP was 78 ± 11 (r: 49-106) mm Hg. Average differences in SBP and DBP among the co-twins (members of a twin pair) were 9 ± 10 (r: 0-40) mm Hg and 8 ± 6 (r: 0-26) mm Hg respectively. Average BMI was 29 ± 8 kg/m 2 . We observed that an average of 3063 (r: 757-7250) CpG islands were differentially methylated (DMRs) between co-twins. Among these DMRs, 10 were associated with average SBP difference and 5 were associated with average DBP difference at a significance level of p < 0.001. DMRs showing the strongest association (unadjusted p < 10 -4 ) between the co-twins were located in the transcriptional start site (TSS) of genes: CDC26 (cell division cycle protein) and NR2F6 (nuclear receptor) for average SBP difference and LEPRE1 (propyl 3 hydroxylase protein) for average DBP difference. Conclusions: BP differences between monozygotic co-twins, which most likely result from environmental factors, appear to be associated with differences in DNA methylation in T lymphocytes.