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July 9, 2008

Homocysteine Levels, Paraoxonase 1 (PON1) Activity, and Cardiovascular Risk—Reply

JAMA. 2008;300(2):168-169. doi:10.1001/jama.300.2.169-a

In Reply: Mr Vos contends that there is no evidence that PON1 possesses antioxidant activity. Rather, he proposes that the homocysteine-thiolactonase activity of PON1 confers the established cardioprotective properties. As stated in our study, we agree that the true physiological function of PON1 remains to be fully elucidated. However, our report of a relationship between a functional PON1 Q192R polymorphism and decreased systemic levels of oxidative stress provides compelling evidence that a genetic determinant of PON1 (either the polymorphism Q192R or another in linkage disequilibrium with it) is associated with systemic indices of oxidant stress. The linkage disequilibrium bin in which the Q192R polymorphism resides lies entirely within the PON1 gene. Thus, the strong association between this polymorphism and systemic measures of oxidative stress argue strongly that PON1 is somehow linked to oxidant stress in vivo.