Association of polymorphisms of THBS2 and HSPA8 with hypertension in Japanese individuals with chronic kidney disease

Abstract

The purpose of the present study was to identify gene polymorphisms that confer susceptibility to hypertension in individuals with chronic kidney disease (CKD), thereby contributing to the prediction of genetic risk for this condition. The study population comprised 1824 Japanese individuals with CKD [estimated glomerular filtration rate (eGFR) <60 ml min-1 1.73 m-2], including 1257 subjects with hypertension and 567 controls. The genotypes for 50 polymorphisms of 46 candidate genes were determined using a method that combines the polymerase chain reaction and sequence-specific oligonucleotide probes with suspension array technology. An initial screen of allele frequencies by the χ2 test revealed that two polymorphisms were significantly (false discovery rate <0.05) associated with the prevalence of hypertension in individuals with CKD. Subsequent multivariable logistic regression analysis with adjustment for age, gender and the prevalence of diabetes mellitus revealed that these two polymorphisms, 3949T↷G (3'-UTR) of the thrombospondin 2 gene (THBS2; odds ratio in recessive model, 8.31) and -110A↷C of the heat shock 70-kDa protein 8 gene (HSPA8; odds ratio in recessive model, 0.72) were significantly (P<0.05) associated with the prevalence of hypertension. The variant G allele of THBS2 was a risk factor for hypertension, whereas the variant C allele of HSPA8 was protective against this condition. A stepwise forward selection procedure also demonstrated that the THBS2 and HSPA8 genotypes were significant (P<0.05) and independent determinants of hypertension. Determination of genotypes for these polymorphisms may prove informative for the prediction of genetic risk for hypertension in Japanese individuals with CKD. Validation of these findings will require additional studies with independent subject panels.