Relationship of paraoxonase-1 Q192R genotypes and in-stent restenosis and re-stenting in Chinese patients after coronary stenting

- Asians have very different genotype distributions of CYP2C19, ABCB1 C3435T, and PON1 Q192R.
- CYP2C19 loss-of-function alleles affect the metabolism of clopidogrel and its antiplatelet response.
- Genetic effects of ABCB1 C3425T and PON1 Q192R on clopidogrel are still controversial.
- Genotype RR of PON1 Q192R was an independent risk factor of re-stenting in Chinese ACS patients after coronary stenting.

Background and aimsAsians have very different genotype distributions of cytochrome P450 2C19 (CYP2C19), ATP-binding cassette, sub-family B, member 1 (ABCB1), and paraoxonase-1 (PON1), in whom relevant studies based on large samples are scarce. The purpose of this study was to evaluate the effects of these genes on outcomes of in-stent restenosis and re-stenting in Chinese patients after coronary stenting.MethodsA total of 2569 acute coronary syndrome (ACS) patients were enrolled in a gene database study. Among the 1674 patients receiving coronary stenting, 504 patients performed repeated coronary angiography within the next year after discharge and were eligible to complete our final cohort.ResultsThe prevalence of the CYP2C19 loss-of-function carriers (had at least 1 allele of *2, *3 and *4) was considerable high (52.2%). During re-angiography, in-stent restenosis occurred in 106 (21.0%) out of the 504 patients; the mean restenosis degree was 71.3% and 152 (30.2%) patients received re-stenting treatment. In multivariate regression, only age and left ventricular ejection fraction (LVEF) were significantly associated with in-stent restenosis. As for predictors of re-stenting, multivariate regression identified variables of LVEF, coronary artery lesions, and PON1 Q192R genotype. Genotype RR of PON1 Q192R was an independent risk factor predicting re-stenting compared with genotypes of QQ and QR (OR 1.95, 95% CI 1.30-2.93, p = 0.001). The genotypes of CYP2C19, ABCB1 C3435T, and PON1 L55M showed no significant associations with in-stent restenosis or re-stenting.ConclusionsGenotype RR of PON1 Q192R was an independent risk factor predicting re-stenting in Chinese ACS patients after coronary stenting.