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CXCL5 polymorphisms are associated with variable blood pressure in cardiovascular disease-free adults.

ABSTRACT: Leukocyte count has been associated with blood pressure, hypertension, and hypertensive complications. We hypothesized that polymorphisms in the CXCL5 gene, which encodes the neutrophilic chemokine ENA-78, are associated with blood pressure in cardiovascular disease (CVD)-free adults and that these polymorphisms are functional.A total of 192 community-dwelling participants without CVD or risk equivalents were enrolled. Two CXCL5 polymorphisms (-156 G?>?C (rs352046) and 398 G?>?A (rs425535)) were tested for associations with blood pressure. Allele-specific mRNA expression in leukocytes was also measured to determine whether heterozygosity was associated with allelic expression imbalance. In -156 C variant carriers, systolic blood pressure (SBP) was 7 mmHg higher than in -156 G/G wild-type homozygotes (131?±?17 vs. 124?±?14 mmHg; P?=?0.008). Similarly, diastolic blood pressure (DBP) was 4 mmHg higher in -156 C variant carriers (78?±?11 vs. 74?±?11 mmHg; P?=?0.013). In multivariate analysis of SBP, age, sex, body mass index, and the -156 G?>?C polymorphism were identified as significant variables. Age, sex, and the -156 G?>?C SNP were further associated with DBP, along with white blood cells. Allelic expression imbalance and significantly higher circulating ENA-78 concentrations were noted for variant carriers.CXCL5 gene polymorphisms are functional and associated with variable blood pressure in CVD-free individuals. The role of CXCL5 as a hypertension- and CVD-susceptibility gene should be further explored.

SUBMITTER: Beitelshees AL

PROVIDER: S-EPMC3505480 | biostudies-literature | 2012 Aug

REPOSITORIES: biostudies-literature

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CXCL5 polymorphisms are associated with variable blood pressure in cardiovascular disease-free adults.

Beitelshees Amber L AL Aquilante Christina L CL Allayee Hooman H Langaee Taimour Y TY Welder Gregory J GJ Schofield Richard S RS Zineh Issam I

Human genomics 20120802

<h4>Objective</h4>Leukocyte count has been associated with blood pressure, hypertension, and hypertensive complications. We hypothesized that polymorphisms in the CXCL5 gene, which encodes the neutrophilic chemokine ENA-78, are associated with blood pressure in cardiovascular disease (CVD)-free adults and that these polymorphisms are functional.<h4>Methods and results</h4>A total of 192 community-dwelling participants without CVD or risk equivalents were enrolled. Two CXCL5 polymorphisms (-156 G ...[more]

PMID: 23245743

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Project description:BackgroundData from before the 2000s indicate that the majority of incident cardiovascular disease (CVD) events occur among US adults with systolic and diastolic blood pressure (SBP/DBP) ≥140/90 mm Hg. Over the past several decades, BP has declined and hypertension control has improved.MethodsWe estimated the percentage of incident CVD events that occur at SBP/DBP <140/90 mm Hg in a pooled analysis of 3 contemporary US cohorts: the REGARDS study (Reasons for Geographic and Racial Differences in Stroke), the MESA (Multi-Ethnic Study of Atherosclerosis), and the JHS (Jackson Heart Study) (n=31 856; REGARDS=21 208; MESA=6779; JHS=3869). Baseline study visits were conducted in 2003 to 2007 for REGARDS, 2000 to 2002 for MESA, and 2000 to 2004 for JHS. BP was measured by trained staff using standardized methods. Antihypertensive medication use was self-reported. The primary outcome was incident CVD, defined by the first occurrence of fatal or nonfatal stroke, nonfatal myocardial infarction, fatal coronary heart disease, or heart failure. Events were adjudicated in each study.ResultsOver a mean follow-up of 7.7 years, 2584 participants had incident CVD events. Overall, 63.0% (95% confidence interval [CI], 54.9-71.1) of events occurred in participants with SBP/DBP <140/90 mm Hg; 58.4% (95% CI, 47.7-69.2) and 68.1% (95% CI, 60.1-76.0) among those taking and not taking antihypertensive medication, respectively. The majority of events occurred in participants with SBP/DBP <140/90 mm Hg among those <65 years of age (66.7%; 95% CI, 60.5-73.0) and ≥65 years of age (60.3%; 95% CI, 51.0-69.5), women (61.4%; 95% CI, 49.9-72.9) and men (63.8%; 95% CI, 58.4-69.1), and for whites (68.7%; 95% CI, 66.1-71.3), blacks (59.0%; 95% CI, 49.5-68.6), Hispanics (52.7%; 95% CI, 45.1-60.4), and Chinese-Americans (58.5%; 95% CI, 45.2-71.8). Among participants taking antihypertensive medication with SBP/DBP <140/90 mm Hg, 76.6% (95% CI, 75.8-77.5) were eligible for statin treatment, but only 33.2% (95% CI, 32.1-34.3) were taking one, and 19.5% (95% CI, 18.5-20.5) met the SPRINT (Systolic Blood Pressure Intervention Trial) eligibility criteria and may benefit from a SBP target goal of 120 mm Hg.ConclusionsAlthough higher BP levels are associated with increased CVD risk, in the modern era, the majority of incident CVD events occur in US adults with SBP/DBP <140/90 mm Hg. While absolute risk and cost-effectiveness should be considered, additional CVD risk-reduction measures for adults with SBP/DBP <140/90 mm Hg at high risk for CVD may be warranted.

Project description:ImportanceHypertension remains the major cardiovascular disease risk factor globally, but variability in measured blood pressure may result in suboptimal management. Whether genetic contributors to elevated blood pressure may complementarily inform cardiovascular disease risk assessment is unknown.ObjectiveTo examine incident cardiovascular disease by blood pressure polygenic risk score independent of measured blood pressures and antihypertensive medication prescriptions.Design, setting, and participantsThe cohort study (UK Biobank) recruited UK residents aged 40 to 69 years between March 2006 and August 2010. Participants without a prior physician diagnosis of cardiovascular disease, including myocardial infarction, stroke, or heart failure, were included. Excluded were individuals with mismatch between self-reported and genotypically inferred sex, sex aneuploidy, missing genotype rates of 1% or greater, and excess genotypic heterozygosity. Data analyses were performed from September 25, 2021, to July 21, 2022.ExposuresMeasured blood pressure and externally derived blood pressure polygenic risk score stratified by hypertension diagnosis and management, which included normal blood pressure (<130/80 mm Hg without antihypertensives), untreated hypertension (systolic blood pressure ≥130 mm Hg or diastolic blood pressure ≥80 mm Hg without antihypertensives), and treated hypertension (current antihypertensives prescriptions).Main outcomes and measuresComposite of first incident myocardial infarction, stroke, heart failure, or cardiovascular-related death.ResultsOf the 331 078 study participants included (mean [SD] age at enrollment, 56.9 [8.1] years; 178 824 female [54.0%]), 83 094 (25.1%) had normal blood pressure, 197 597 (59.7%) had untreated hypertension, and 50 387 (15.2%) had treated hypertension. Over a median (IQR) follow-up of 11.1 (10.4-11.8) years, the primary outcome occurred in 15 293 participants. Among those with normal blood pressure, untreated hypertension, and treated hypertension, each SD increase in measured systolic blood pressure was associated with hazard ratios of 1.08 (95% CI, 0.93-1.25), 1.20 (95% CI, 1.16-1.23), and 1.16 (95% CI, 1.11-1.20), respectively, for the primary outcome. Among these same categories, each SD increase in genetically predicted systolic blood pressure was associated with increased hazard ratios of 1.13 (95% CI, 1.05-1.20), 1.04 (95% CI, 1.01-1.07), and 1.06 (95% CI, 1.02-1.10), respectively, for the primary outcome independent of measured blood pressures and other covariates. Findings were similar for measured and genetically predicted diastolic blood pressure.Conclusions and relevanceBlood pressure polygenic risk score may augment identification of individuals at heightened cardiovascular risk, including those with both normal blood pressure and hypertension. Whether it may also guide antihypertensive initiation or intensification requires further study.

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CXCL5 polymorphisms are associated with variable blood pressure in cardiovascular disease-free adults.

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CXCL5 polymorphisms are associated with variable blood pressure in cardiovascular disease-free adults.

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