High expressor paraoxonase PON1 gene promoter polymorphisms are associated with reduced risk of vascular disease in younger coronary patients.
Human paraoxonase-1 is hypothesised to protect serum lipoproteins from oxidative stress. Decreased serum activity of paraoxonase-1 in animal models is associated with an increased risk of vascular disease and has been linked to the anti-oxidant capacity of the enzyme. Promoter polymorphisms of the human paraoxonase-1 gene strongly influence serum concentrations of the enzyme. The present study examined the hypothesis that promoter polymorphisms may be genetic risk factors for vascular disease in man. Genotypes arising from the promoter C(-907)G polymorphism were analysed in the ECTIM2 population. The global odds ratio for myocardial infarction, comparing the high expressor GG genotype to other genotypes, was 0.77 (0.61-0.97) (P=0.024). The association with the promoter genotype was more pronounced in the youngest age group (odds ratio 0.52 (0.31-0.87), P=0.012) and was progressively lost with age (respectively 50 years to <60 years, P=0.26; >60 years, P=0.45). There was no association between the promoter genotypes and serum lipids. The data are consistent with the high expressor promoter genotype being linked to reduced risk of myocardial infarction. The influence of the genotype may be compromised in older patients.
Leviev
Ilia
I
Clinical Diabetes Unit, Division of Endocrinology and Diabetes, University Hospital, 24, rue Micheli-du-Crest, 1211 Geneva 14, Switzerland.
Poirier
Odette
O
Nicaud
Viviane
V
Evans
Alun
A
Kee
Frank
F
Arveiler
Dominique
D
Morrisson
Caroline
C
Cambien
François
F
James
Richard W
RW
D000328:Adult; D043303:Aryldialkylphosphatase; D001483:Base Sequence; D016022:Case-Control Studies; D015331:Cohort Studies; D016001:Confidence Intervals; D003327:Coronary Disease / Q000150:complications / Q000453:epidemiology / Q000235:genetics*; D004950:Esterases / Q000235:genetics*; D005260:Female; D005819:Genetic Markers; D005838:Genotype; D006801:Humans; D016014:Linear Models; D008297:Male; D008875:Middle Aged; D008969:Molecular Sequence Data; D016017:Odds Ratio; D016133:Polymerase Chain Reaction; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012016:Reference Values; D018570:Risk Assessment; D012307:Risk Factors; D014652:Vascular Diseases / Q000150:complications / Q000235:genetics*
D005819:Genetic Markers; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human