Paraoxonase-1 promoter polymorphism C--107T and serum apolipoprotein AI interact to modulate serum paraoxonase-1 status.
OBJECTIVE
The objective was to examine the hypothesis that modifications to paraoxonase-1 specific activity (SP, activity per unit mass peptide) could contribute to serum paraoxonase-1 status, a determinant of the clinical efficacy of the enzyme.


METHODS
Enzyme activities and concentrations were determined in a large population (n=912) of patients and controls. SP were subsequently examined as a function of paraoxonase-1 gene polymorphisms, plasma lipids and lipoproteins, and physiological and pathophysiological parameters.


RESULTS
Pathophysiological parameters (diabetes, metabolic syndrome, smoking, aging) did not promote variations in paraoxonase-1 SP, whilst coronary disease lowered SP (P<0.003). No serum lipid, apolipoprotein or lipoprotein component had an impact on specific activity, with the exception of apolipoprotein AI (P<0.005, both substrates). The paraoxonase-1 promoter C--107T and Q192R polymorphisms influenced SP and, together with apolipoprotein AI, were highly significant, independent determinants in regression models. There was an interaction between apolipoprotein AI and the C--107T polymorphism, which significantly modulated SP and serum paraoxonase-1 status.


CONCLUSIONS
Enzyme inactivation giving rise to modulated activity per unit mass of peptide is not a major contributor to pathological effects of disease on serum paraoxonase-1 status. The C--107T polymorphism and serum apolipoprotein AI have major impacts individually on SP and also provide an example of gene-environment interaction to modulate such activities. These effects accentuate the differences between--107C and--107T allele carriers in terms of serum paraoxonase-1 status. The data underline the complexity of the factors that determine serum paraoxonase-1 status and suggest that the latter would benefit from therapeutic modulation of serum high density lipoproteins.
James
Richard W
RW
Clinical Diabetes Unit, Division of Endocrinology, Diabetes and Nutrition, University Hospital, 1211 Geneva 14, Switzerland. Richard.James@hcuge.ch
Kalix
Barbara
B
Bioletto
Silvana
S
Brulhart-Meynet
Marie-Claude
MC
D016632:Apolipoprotein A-I / Q000097:blood*; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D006801:Humans; D015999:Multivariate Analysis; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic
D016632:Apolipoprotein A-I; D043303:Aryldialkylphosphatase