Abstract P101: Genetic Variation of Phenylethanolamine-N-methyltransferase Influences Cardiovascular Function in Healthy Humans
Objectives: Genetic susceptibility to hypertension can be caused by alterations in cardiovascular and/or renal function. Previous work using genome-wide association studies have demonstrated that the gene that encodes phenylethanolamine-N-methyltransferase (PNMT) is a candidate for hypertension. Follow-up studies confirmed that the gene that encodes PNMT may alter susceptibility to hypertension in African Americans, although no mechanistic data was assessed. Genetic variation of PNMT alters the catecholamine response to exercise, and variation of PNMT at position -182 has been associated with susceptibility to multiple sclerosis.
Methods: We sought to determine the influence of genetic variation of PNMT (A-182G) on renal Na+ handling and cardiovascular function in humans. We collected serum epinephrine (Epi) and norepinephrine (NE), 24-hour urine, serum Na+, K+, and creatinine, and measured cardiac output (Q, acetylene rebreathing), heart rate (HR, 12-lead EKG), blood pressure (systolic, SBP, diastolic, DBP, and calculated mean arterial, MAP) and calculated fractional excretion of Na+ (FENa), stroke volume (SV), and systemic vascular resistance (SVR) in 20 normotensive subjects (n: AA=6 and GG=14).
Results: We found that the GG genotype had higher Epi and Epi/NE when compared to AA (Epi=98±21 vs. 53±10pg/l; NE= 344±56 vs. 462±79pg/l; Epi/NE= 0.31±0.07 vs. 0.13±0.03, for GG and AA, respectively, mean±SE, p<0.05 for Epi and Epi/NE). We found no differences between the genotype groups in 24hr. renal Na+ handling (serum Na+, urine Na+, or FENa). We found no differences in HR, SBP, or SV between the groups. The GG group had a trend towards a lower DBP, and MAP, but these did not reach statistical significance (DBP= 70±3 vs. 75±2mmHg; MAP= 83±3 vs. 87±2mmHg, for GG and AA, respectively, mean±SE). The GG group had a higher Q and a lower SVR when compared to the AA group (Q= 6.0±0.5 vs. 4.8±0.4 l/min; SVR= 1020±64 vs. 1316±95 dynes*sec/cm5, for GG and AA, respectively mean±SE, p<0.05).
Conclusion: These results suggest that genetic variation of PNMT can influence resting blood pressure in normotensive individuals and that this may be the result of cardiovascular function, rather than renal Na+ handling.
- © 2011 by American Heart Association, Inc.