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The Combined Effect of Paraoxonase Promoter and Coding Region Polymorphisms on the Risk of Arterial Ischemic Stroke Among Young Adults
Barbara Voetsch, MD, PhD;
Kelly S. Benke, AB;
Carolien I. Panhuysen, MD, PhD;
Benito P. Damasceno, MD, PhD;
Joseph Loscalzo, MD, PhD
Arch Neurol. 2004;61:351-356.
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.
Conclusion 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.
From the Whitaker Cardiovascular Institute (Drs Voetsch and Loscalzo) and the Genetics Program (Ms Benke and Dr Panhuysen), Evans Department of Medicine, Boston University School of Medicine, Boston, Mass; and the Department of Neurology, State University of Campinas, Campinas, São Paulo, Brazil (Drs Voetsch and Damasceno).
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