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.

METHODS AND 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.

CONCLUSION

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.