The combined effect of paraoxonase promoter and coding region polymorphisms on the risk of arterial ischemic stroke among young adults.
BACKGROUND
Serum paraoxonase (PON1) is a high-density lipoprotein-associated esterase with antioxidant and antiatherogenic properties that has recently been implicated in the pathogenesis of cardiovascular disease. Interindividual variability in PON1 levels is determined by the Q192R and L55M coding region polymorphisms and by 2 recently described polymorphisms in the promoter of the PON1 gene, C(-107)T and G(-824)A.


OBJECTIVE
To determine the association of the PON1 promoter polymorphisms with arterial ischemic stroke (AIS) in the young. DESIGN. SETTING, AND PATIENTS: We studied 118 young patients (age, <45 years) with a first nonfatal AIS of undetermined etiology and 118 control subjects, matched simultaneously for age and sex. The PON1 C(-107)T polymorphism was determined by single-stranded conformational polymorphism analysis and the G(-824)A substitution by polymerase chain reaction and restriction enzyme digestion.


RESULTS
The presence of the low-expressor -107T allele was associated with an independent increase in overall risk of AIS (odds ratio [OR], 2.69; 95% confidence interval [CI], 1.06-6.78; P =.04) by conditional multiple logistic regression analysis. Among individuals with the 192RR genotype, the presence of the -107T allele led to a higher but nonsignificant risk, yielding an OR of 4.15 (95% CI, 0.35-48.76; P =.15) when compared with noncarriers of the T allele and 17.01 (95% CI, 1.74-166.35; P =.02) when compared with noncarriers of either variant. No significant difference between groups was found regarding the G(-824)A polymorphism.


CONCLUSIONS
These findings suggest that the PON1 -107T allele is independently associated with the risk of AIS, in addition to interacting with and potentiating the risk conferred by the Q192R polymorphism.
Voetsch
Barbara
B
Whitaker Cardiovascular Institute, Evans Department of Medicine, Boston University School of Medicine, MA 02118, USA.
Benke
Kelly S
KS
Panhuysen
Carolien I
CI
Damasceno
Benito P
BP
Loscalzo
Joseph
J
D000328:Adult; D001120:Arginine / Q000235:genetics; D043303:Aryldialkylphosphatase / Q000097:blood / Q000235:genetics*; D016022:Case-Control Studies; D016001:Confidence Intervals; D003710:Demography; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D005973:Glutamine / Q000235:genetics; D006801:Humans; D016015:Logistic Models; D008297:Male; D016017:Odds Ratio; D016366:Open Reading Frames; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D011401:Promoter Regions, Genetic; D012306:Risk; D017422:Sequence Analysis, DNA / Q000379:methods; D020521:Stroke / Q000097:blood / Q000235:genetics*
D005973:Glutamine; D001120:Arginine; D043303:Aryldialkylphosphatase