CXCL5 gene polymorphisms are related to systemic concentrations and leukocyte production of epithelial neutrophil-activating peptide (ENA-78).
Data exist linking elevated epithelial neutrophil activating peptide (ENA-78) concentrations with myriad inflammatory conditions. ENA-78 is encoded by the CXCL5 gene which has recently been shown to be polymorphic in nature (rs352046 and rs425535). No functional data on these polymorphisms exist. We investigated whether CXCL5 polymorphisms are associated with differences in plasma ENA-78 concentrations or leukocyte production of ENA-78 from cultured leukocytes in relatively healthy adults. We genotyped 114 adults for the above polymorphisms. Variant alleles at both loci were highly linked (D'=1, r2=0.94). The rs352046 variant allele was associated with significantly higher ENA-78 plasma concentrations. A genotype effect was also demonstrated for this polymorphism and leukocyte production of ENA-78. Both polymorphisms were predicted to have functional consequences by in silico analyses, with the rs352046 polymorphism found to occur at a transcription factor binding site for myeloid zinc finger proteins and the rs425535 polymorphism found to be located in an exon splicing enhancer site. Our findings add to the strength of CXCL5 as candidate gene in future disease-gene and pharmacogenetic association studies.
Zineh
Issam
I
University of Florida College of Pharmacy, Department of Pharmacy Practice, 1600 SW Archer Road., Room PG-06, PO Box 100486, Gainesville, FL 32610, USA. zineh@cop.ufl.edu
Aquilante
Christina L
CL
Langaee
Taimour Y
TY
Beitelshees
Amber L
AL
Arant
Christopher B
CB
Wessel
Timothy R
TR
Schofield
Richard S
RS
D000328:Adult; D000483:Alleles; D054365:Chemokine CXCL5; D019743:Chemokines, CXC / Q000737:chemistry* / Q000235:genetics*; D005260:Female; D016678:Genome; D005838:Genotype; D006720:Homozygote; D006801:Humans; D007249:Inflammation; D007962:Leukocytes / Q000378:metabolism*; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic
C486263:CXCL5 protein, human; D054365:Chemokine CXCL5; D019743:Chemokines, CXC