Kelley, Eli F.

Purpose: The purpose of this study was to determine the effectiveness of a simple algorithm to mathematically predict a patients’ response to blood pressure (BP) therapy using functional genes in the 3 major organ systems involved in hypertension. Methods: Eighty-six patients with controlled hypertension completed 1 study visit consisting of a buccal swab collection, measurement of office BP, and a medical chart review for BP history. Genes in the analysis included 14 functional alleles in 11 genes. These genotypes were mathematically summed per organ system to determine whether a patient would likely respond to target therapy. Results: Patients recommended to and taking a diuretic had significantly higher rates of control (<120/<80) than patients recommended but not taking this drug class (0.2 ± 0.1 and 0.03 ± 0.03, respectively). Furthermore, there was a difference between patients genetically recommended and taking an angiotensin receptor blocker (ARB) vs patients recommended but not taking an ARB for the lowest diastolic blood pressure (DBP) and mean arterial pressure (MAP) recorded in the past 2 years (DBP = 66.2 ± 2.9 and 75.3 ± 1.7, MAP = 82.3 ± 2.8 and 89.3 ± 1.5, respectively). In addition, there was a nonsignificant trend for greater reductions in ΔSBP, ΔDBP, and ΔMAP in patients on recommended drug class for beta-blockers, diuretics, and angiotensin II receptor blockers vs patients not on these classes. Conclusion: The present study suggests that simple mathematical weighting of functional genotypes known to control BP may be ineffective in predicting control. This study demonstrates the need for a more complex, weighted, multigene algorithm to more accurately predict BP therapy response.

Hypertension (HTN) is a complex disease with interactions among multiple organ systems, including the heart, vasculature, and kidney with a strong heritable component. Despite the multifactorial nature of HTN, no clinical guidelines utilize a multi-gene approach to guide blood pressure (BP) therapy. Non-smokers with a family history of HTN were included in the analysis (n = 384; age = 61.0 ± 0.9, 11% non-white). A total of 17 functional genotypes were weighted according to the previous effect size in the literature and entered into an algorithm. Pharmacotherapy was ranked from 1–4 as most to least likely to respond based on the algorithmic assessment of individual patient’s genotypes. Three-years of data were assessed at six-month intervals for BP and medication history. There was no difference in BP at diagnosis between groups matching the top drug recommendation using the multi-gene weighted algorithm (n = 92) vs. those who did not match (n = 292). However, from diagnosis to nadir, patients who matched the primary recommendation had a significantly greater drop in BP when compared to patients who did not. Further, the difference between diagnosis to current 1-year average BP was lower in the group that matched the top recommendation. These data suggest an association between a weighted multi-gene algorithm on the BP response to pharmacotherapy.

Abstract Kelley, EF, Johnson, BD, and Snyder, EM. Beta-2 adrenergic receptor genotype influences power output in healthy subjects. J Strength Cond Res 31(8): 2053–2059, 2017—The purpose of this study was to determine the effects of ADRB2 genotypes on muscle function (absolute power and relative power) in healthy subjects. We performed genotyping of the ADRB2 (amino acid 16) and high-intensity, steady-state exercise on 77 healthy subjects (AA = 18, AG = 25, GG = 34). There were no differences between genotype groups in age, height, weight, or body mass index (BMI) (age = 28.9 ± 5.7 years, 27.9 ± 5.7 years, 29.2 ± 5.9 years, height = 170.7 ± 8.6 cm, 174.9 ± 8.7 cm, 173.4 ± 9.6 cm, weight = 68.5 ± 13.0 kg, 75.0 ± 12.9 kg, 74.4 ± 12.9 kg, and BMI = 23.4 ± 3.9, 24.4 ± 2.9, 24.7 ± 3.4, for AA, AG, and GG, respectively). The genotype groups differed significantly in watts, and watts/V̇ o 2 with heavy exercise (watts = 186.3 ± 54.6, 237.8 ± 54.4, 219.4 ± 79.5, watts/V̇ o 2 = 0.08 ± 0.006, 0.09 ± 0.005, 0.08 ± 0.006). There was a trend toward significance ( p = 0.058) for W·kg −1 (2.7 ± 0.4, 3.2 ± 0.5, 2.9 ± 0.8, for AA, AG, and GG, respectively). These data suggest that genetic variation of the ADRB2 may influence relative strength in healthy subjects and may become an important genetic determinant of muscular strength and functional capacity in patients with diseases that result in a loss of muscle strength.