Association of a polymorphism of ROR2 and ischemic stroke in Japanese individuals with chronic kidney disease

Abstract

Although chronic kidney disease (CKD) is recognized as an important risk factor for ischemic stroke, genetic factors underlying predisposition to ischemic stroke in individuals with or without CKD remain largely unknown. The aim of the present study was to identify genetic variants that confer susceptibility to ischemic stroke in individuals with or without CKD in order to allow prediction of genetic risk for such individuals separately. The study population comprised 974 individuals with CKD, including 227 subjects with ischemic stroke and 747 controls, and 3,470 individuals without CKD, including 612 subjects with ischemic stroke and 2,858 controls. The 150 polymorphisms examined in the present study were selected by genome-wide association studies of ischemic stroke and myocardial infarction with the use of the GeneChip Human Mapping 500K Array Set (Affymetrix). In individuals with CKD, an initial Chi-square test revealed that the A↷G polymorphism (rs10992119) of the receptor tyrosine kinase-like orphan receptor 2 gene (ROR2) was significantly (false discovery rate for allele frequency, 0.0478) associated with ischemic stroke. Multivariable logistic regression analysis with adjustment for covariates revealed that the A↷G polymorphism of ROR2 was significantly (P=0.0100) associated with ischemic stroke (recessive model; odds ratio 1.57; 95% CI 1.12-2.23), with the G allele representing a risk factor for this condition. A stepwise forward selection procedure demonstrated that this polymorphism was a significant (P=0.0095) and independent determinant of ischemic stroke. In individuals without CKD, no polymorphism was significantly related to ischemic stroke. Genotyping for ROR2 may prove informative for assessment of the genetic risk for ischemic stroke in Japanese individuals with CKD. Determination of the genotype for this polymorphism may prove informative for assessment of the genetic risk for ischemic stroke in such individuals.