Myeloperoxidase genetic polymorphisms modulate human neutrophil enzyme activity: genetic determinants for atherosclerosis?
OBJECTIVE
Myeloperoxidase (MPO), an abundant leukocyte hemoprotein has been linked to atherosclerosis and cardiovascular disease. We previously found new genetic polymorphisms in MPO gene. The purpose of this study was to evaluate the influences of these polymorphisms on human neutrophil MPO activity by means of haplotype analysis.


RESULTS
Neutrophils from 102 blood donors were isolated and MPO activity was measured, while subjects were genotyped for polymorphisms located in MPO gene 5'non-coding region (-1940A > G, -638C > A, -463G > A and -129G > A) and in coding region (V53F, M251T, A332V, I642L and I717V). Single-point analysis showed that the -638C > A and the V53F polymorphisms were significantly associated with MPO activity, and haplotype analysis confirmed that two haplotypes, one carrying the -638A allele and the other carrying the 53F allele, resulted an increase in MPO activity.


CONCLUSIONS
Since MPO is suspected to be a bio-marker in cardiovascular disease, -638C > A and V53F polymorphisms associated with increased enzymatic activity could be genetic determinants for cardiovascular disease risk.
Chevrier
Isabelle
I
Université Paris-Descartes, Faculté de Médecine, INSERM UMRS 490, 45 rue des Saints-Pères, 75270 Paris Cedex 06, France.
Tregouet
David-Alexandre
DA
Massonnet-Castel
Simone
S
Beaune
Philippe
P
Loriot
Marie-Anne
MA
D000483:Alleles; D050197:Atherosclerosis / Q000175:diagnosis / Q000235:genetics; D015415:Biomarkers / Q000032:analysis; D003324:Coronary Artery Disease / Q000175:diagnosis* / Q000235:genetics; D006801:Humans; D009504:Neutrophils / Q000201:enzymology*; D009195:Peroxidase / Q000032:analysis* / Q000235:genetics*; D011110:Polymorphism, Genetic
D015415:Biomarkers; D009195:Peroxidase