Lack of Association Between Genetic Variations in CYP3A5 and Blood Pressure or Hypertension Risk in the UK Biobank

Pia LeiboldChristelle LteifJulio Duarte^*

• University of Florida, Gainesville, United States

Hypertension (HTN) is a leading risk factor for several cardiovascular diseases. While some previous studies reported that CYP3A5 variants were associated with decreased blood pressure and risk of HTN, others reported no associations. We aimed to analyze the association of CYP3A5 variants (*3, *6, *7) and CYP3A5 activity with systolic blood pressure (SBP), diastolic blood pressure (DBP), mean arterial pressure (MAP), and HTN diagnosis in the UK Biobank (N=487,171), a population large enough to have sufficient power to detect clinically meaningful associations. Linear and logistic regression models were used, adjusting for age, sex, race, antihypertensives use, smoking status, and salt intake. Moreover, subgroup analyses were performed in Black patients, White patients, patients of East Asian and South Asian descent separately, using the same models. Neither the CYP3A5 variants, nor the CYP3A5 activity showed significant associations with SBP, DBP, MAP, or HTN. In a sensitivity analysis based on different racial subgroups, only White patients showed significant association between the CYP3A5*3 variant and slightly higher DBP (β = 0.10 mmHg, 95% CI: 0.02 to 0.18, P = 0.01), as well as between genotype-predicted CYP3A5 activity score and slightly lower DBP (β = -0.10 mmHg, 95% CI: -0.18 to -0.02, P = 0.01). While these associations were statistically significant, the small effect sizes and lack of associations observed in the whole UK Biobank population suggest that CYP3A5 variation likely has no impact on blood pressure related phenotypes in a general population.