Susceptibility of PON1/PON2 Genetic Variations to Ischemic Stroke Risk in a Chinese Han Population.

Abstract

BackgroundParaoxonases (PONs) are a family of orphan enzymes with multiple functions, including anti-inflammatory, antioxidative, antiatherogenic activities. Studies have suggested that genetic variations in PON1 and PON2 are associated with ischemic stroke (IS) risk; however, the conclusion remains unclear in the Chinese population.MethodsTo investigate the susceptibility of genetic variations in PON1 and PON2 to risk of IS and its subtypes, this case–control study was carried out on a Chinese population comprising 300 IS patients and 300 healthy controls. Genotypes of six genetic variations in PON1 and PON2 were identified with an improved multiplex ligase detection–reaction technique.ResultsPON1 rs662 was associated with increased risk of IS (CT vs. TT — ORadjusted 1.79, 95% CI 1.08–2.97; p=0.025). Stratified analysis for patients by sex revealed that the significant association of PON1 rs662 with IS risk was maintained in the male cohort (CT vs. TT — ORadjusted 2.59, 95% CI 1.29–5.21 [p=0.009]; CT/CC vs. TT — ORadjusted 2.03, 95% CI 1.05–3.93 [p=0.036]), but not in the female cohort. Analysis according to IS subtype revealed that PON1 rs662 genetic variation was an increased risk in the subcohort of patients with large-artery atherosclerosis (CT/CC vs. TT — ORadjusted 2.31, 95% CI 1.09–4.91; p=0.029), but not in patients with other types of IS.ConclusionThis study suggested that PON1 rs662 presented a potential risk of IS, especially for males, and this association was more obvious for large-artery atherosclerosis.