title: CXCL5 polymorphisms are associated with variable blood pressure in cardiovascular disease-free adults.
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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Division of Endocrinology, Diabetes and Nutrition, University of Maryland School of Medicine, Baltimore, MD 21201, USA. abeitels@medicine.umaryland.edu
authors.forename: Amber L
authors.initials: AL
authors.lastname: Beitelshees
authors.forename: Christina L
authors.initials: CL
authors.lastname: Aquilante
authors.forename: Hooman
authors.initials: H
authors.lastname: Allayee
authors.forename: Taimour Y
authors.initials: TY
authors.lastname: Langaee
authors.forename: Gregory J
authors.initials: GJ
authors.lastname: Welder
authors.forename: Richard S
authors.initials: RS
authors.lastname: Schofield
authors.forename: Issam
authors.initials: I
authors.lastname: Zineh
mesh_terms: D000328:Adult; D000483:Alleles; D015415:Biomarkers / Q000097:blood; D001794:Blood Pressure / Q000235:genetics*; D001823:Body Composition; D015992:Body Mass Index; D054365:Chemokine CXCL5 / Q000097:blood / Q000235:genetics*; D005260:Female; D056426:Genetic Loci; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D006973:Hypertension / Q000235:genetics*; D007962:Leukocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D015999:Multivariate Analysis; D020641:Polymorphism, Single Nucleotide; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D017422:Sequence Analysis, DNA
chemical_list: D015415:Biomarkers; C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D012333:RNA, Messenger