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

Hum Genomics. 2012 Aug 2;6(1):9. doi: 10.1186/1479-7364-6-9.

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.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Alleles
  • Biomarkers / blood
  • Blood Pressure / genetics*
  • Body Composition
  • Body Mass Index
  • Chemokine CXCL5 / blood
  • Chemokine CXCL5 / genetics*
  • Female
  • Genetic Loci
  • Heterozygote
  • Homozygote
  • Humans
  • Hypertension / genetics*
  • Leukocytes / metabolism
  • Male
  • Middle Aged
  • Multivariate Analysis
  • Polymorphism, Single Nucleotide*
  • RNA, Messenger / genetics
  • RNA, Messenger / metabolism
  • Sequence Analysis, DNA

Substances

  • Biomarkers
  • CXCL5 protein, human
  • Chemokine CXCL5
  • RNA, Messenger