Email updates

Keep up to date with the latest news and content from Human Genomics and BioMed Central.

Open Access Primary research

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

Amber L Beitelshees1*, Christina L Aquilante2, Hooman Allayee3, Taimour Y Langaee4, Gregory J Welder4, Richard S Schofield5 and Issam Zineh4

Author Affiliations

1 Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, 660 W. Redwood St, HH469, Baltimore, MD, 21201, USA

2 Department of Pharmaceutical Sciences, University of Colorado Skaggs School of Pharmacy and Pharmaceutical Sciences, Aurora, CO, 80045, USA

3 Department of Preventive Medicine and Institute for Genetic Medicine, Keck School of Medicine, University of Southern California, Los Angeles, CA, 90089, USA

4 Department of Pharmacotherapy and Translational Research, Center for Pharmacogenomics, University of Florida College of Pharmacy, Gainesville, FL, 32610, USA

5 Division of Cardiovascular Medicine and Department of Veterans Affairs Medical Center, University of Florida College of Medicine, Gainesville, FL, 32603, USA

For all author emails, please log on.

Human Genomics 2012, 6:9  doi:10.1186/1479-7364-6-9

Published: 2 August 2012

Abstract

Objective

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.

Methods and results

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.

Conclusion

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.

Keywords:
CXCL5; ENA-78; Blood pressure; Hypertension; Leukocytes