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

BACKGROUND: Paraoxonases (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. METHODS: To 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. RESULTS: PON1 rs662 was associated with increased risk of IS (CT vs. TT — OR(adjusted) 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 — OR(adjusted) 2.59, 95% CI 1.29–5.21 [p=0.009]; CT/CC vs. TT — OR(adjusted) 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 — OR(adjusted) 2.31, 95% CI 1.09–4.91; p=0.029), but not in patients with other types of IS. CONCLUSION: This study suggested that PON1 rs662 presented a potential risk of IS, especially for males, and this association was more obvious for large-artery atherosclerosis.