Association of genetic variants with chronic kidney disease in Japanese individuals with or without hypertension or diabetes mellitus

Abstract

Hypertension and diabetes mellitus are important risk factors for chronic kidney disease (CKD). The purpose of the present study was to identify genetic variants that confer susceptibility to CKD in individuals with or without hypertension or diabetes mellitus, thereby contributing to the personalized prevention of CKD in such individuals separately. The study population comprised 5835 unrelated Japanese individuals, including 1763 subjects with CKD and 4072 controls. The 150 polymorphisms 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). The genotypes for these polymorphisms were determined by a method that combines polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. The χ(2) test, multivariable logistic regression analysis with adjustment for covariates, as well as a stepwise forward selection procedure revealed that two different polymorphisms were significantly (P<0.005) associated with the prevalence of CKD in individuals with or without hypertension or diabetes mellitus: the A→G (Lys625Arg) polymorphism of CDH4 (rs6142884) in individuals without diabetes mellitus, and the C→T polymorphism of PTPRN2 (rs1638021) in individuals with hypertension and diabetes mellitus. No polymorphism was significantly associated with CKD in individuals with or without hypertension, in those with diabetes mellitus, or in those without hypertension or diabetes mellitus. Stratification of subjects based on hypertension or diabetes mellitus may thus be fundamental to achieving the personalized prevention of CKD with the use of genetic information.