The paraoxonase PON1 promoter polymorphism C(-107)T is associated with increased serum glucose concentrations in non-diabetic patients.
OBJECTIVE
Oxidative stress could contribute to diabetes and its complications by predisposing to insulin resistance. Lipid peroxidation products are thought to be one mechanism involved in reduced insulin sensitivity. The serum enzyme, paraoxonase-1, protects lipoprotein lipids from oxidation. We examined the hypothesis that paraoxonase-1 could be associated with abnormal serum glucose concentrations in non-diabetic patients.


METHODS
Serum paraoxonase-1 activities and concentrations, as well as paraoxonase-1 gene polymorphisms, were analysed as a function of fasting glucose concentrations in non-diabetic patients and in Type II (non-insulin-dependent) diabetic patients.


RESULTS
Serum paraoxonase-1 activities and concentrations were lower (p <0.05) in non-diabetic patients with abnormal fasting glucose concentrations. It was due to a higher frequency of low expressor paraoxonase-1 promoter genotypes in patients with abnormal glucose control. Promoter polymorphisms were independent determinants of abnormal fasting glucose concentrations. Low expressor genotypes were associated with higher glucose concentrations in non-diabetic patients (p = 0.046) and a trend to higher concentrations in Type II diabetic patients. The coding region paraoxonase-1 polymorphisms L55 M and Q192R was not associated with differences in fasting glucose. CONCLUSION/INTERPRETATION. The promoter polymorphism C(-107)T is a marker for abnormal fasting glucose concentrations in non-diabetic patients. It could indicate an active role for paraoxonase-1, possibly pre-disposing to insulin resistance, or linkage of paraoxonase-1 polymorphisms with other gene products implicated in glucose metabolism.
Leviev
I
I
Clinical Diabetes Unit, Division of Endocrinology and Diabetology, University Hospital, Geneva, Switzerland.
Kalix
B
B
Brulhart Meynet
M C
MC
James
R W
RW
D000368:Aged; D043303:Aryldialkylphosphatase; D001786:Blood Glucose / Q000032:analysis*; D015992:Body Mass Index; D008076:Cholesterol, HDL / Q000097:blood; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics; D004950:Esterases / Q000097:blood / Q000235:genetics*; D005215:Fasting; D005260:Female; D006720:Homozygote; D006801:Humans; D015227:Lipid Peroxidation / Q000235:genetics; D016015:Logistic Models; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D014280:Triglycerides / Q000097:blood
D001786:Blood Glucose; D008076:Cholesterol, HDL; D014280:Triglycerides; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human