Abstract P069: White Cell Gene Expression Related To Immune Function And Cumulative Blood Pressure During Young Adulthood And Middle Age: Coronary Artery Risk Development In Young Adults (CARDIA)

Abstract

Introduction: High blood pressure (BP) is a global public health problem that is strongly associated with many aspects of cardiovascular disease. Approximately 90% of hypertension cases have unknown cause. Studies of white blood cell gene expression may help to clarify the pathobiology. Methods: Gene expression (25 genes) was assayed in CARDIA at the Year 25 Exam (N=3,074 black and white men and women in 4 US cities, examined in 2010-2011, age 42-56 years). Whole blood was collected in PAXgene Blood RNA tubes; mRNA was isolated using the PAXgene Blood RNA kit (Qiagen Inc., Germantown, MD). The nCounter analysis system (Nanostring Inc., Seattle, WA) was used to measure expression of 25 genes related to inflammation and oxidative stress. Gene expression levels were logarithmically (base 2) transformed to approximate a normal distribution, so 1 unit higher represents doubling of the expression. Average cumulative sitting rest BP exposure was calculated (N=2,823) as the time weighted average across ≥5 BP measurements among 9 CARDIA exams with ≥1 measurement in each of Set 1 Years 0, 2, 5, 7; Set 2 Years 10, 15; and Set 3 Years 20, 25, 30. We added 10 mmHg to the systolic BP and 5 mmHg to the diastolic BP at visits in which antihypertensive medications were used. Linear regression estimated associations between dependent variables cumulative systolic and diastolic BP and each of the 25 gene expression levels, adjusting for age, race, sex, clinic, and year 25 body mass index. Hypertension at year 25 was defined as BP >140/90 mmHg or taking antihypertensive medications and pre-hypertension at year 25 was defined as BP between 121-139/81-90 mmHg, not taking antihypertensive medications. Unconditional logistic regression models were used to estimate the cross sectional association between hypertension and gene expression after adjusting for the covariates mentioned above. Results: The mean ± standard deviation for cumulative systolic BP was 113±11 mm Hg and for cumulative diastolic BP was 72±8 mmHg. NADH Dehydrogenase [Ubiquinone] 1 Beta Subcomplex Subunit 3 ( NDUFB3) , a mitochondrial gene involved in the electron transport chain was significantly associated with both cumulative systolic (β=1.549; p<0.0001) and diastolic BP measures (β=1.281 mmHg/1 log 2 unit of expression; p<0.0001), even after Bonferroni correction. Other genes had weaker signals. Consistent with these observations, hypertension (n=898) at year 25 (OR: 1.737; p<0.001) and pre-hypertension (n=1,127) at year 25 (OR:1.288; p=0.005) were also associated with increased NDUFB3 expression. Conclusions: Expression of the NDUFB3 gene, an element of oxidative stress, was associated with BP assessed throughout young adult and middle age and with concurrent hypertension.