Association of genetic variants with chronic kidney disease in individuals with different lipid profiles

Abstract

The purpose of the present study was to identify genetic variants that confer susceptibility to chronic kidney disease (CKD) in individuals with low or high serum concentrations of triglycerides (TG), high-density lipoprotein (HDL)-cholesterol, or low-density lipoprotein (LDL)-cholesterol, thereby contributing to the personalized prevention of CKD in such individuals. The study population comprised 5944 Japanese individuals, including 1706 subjects with CKD [estimated glomerular filtration rate (eGFR) <60 ml/min/1.73 m2] and 4238 controls (eGFR ≥60 ml/min/1.73 m2). The genotypes for 296 polymorphisms of 202 candidate genes were determined. The Chi-square test, multivariable logistic regression analysis with adjustment for covariates, and a stepwise forward selection procedure revealed that seven different polymorphisms were significantly (P<0.005) associated with the prevalence of CKD in individuals with low or high serum concentrations of TG or HDL- or LDL-cholesterol: the A→G (Glu23Lys) polymorphism of KCNJ11 and the 125592C→A (Thr431Asn) polymorphism of ROCK2 in individuals with low serum TG; the 734C→T (Thr254Ile) polymorphism of ACAT2 and the C→G (Gln27Glu) polymorphism of ADRB2 in individuals with high serum TG; the -1607/1G→2G polymorphism of MMP1 in individuals with low serum HDL-cholesterol; the G→A (Val158Met) polymorphism of COMT in individuals with low serum LDL-cholesterol; the 584G→A (G1n192Arg) polymorphism of PON1 in individuals with high serum LDL-cholesterol. No polymorphism was associated with CKD in individuals with high serum HDL-cholesterol. These results suggest that polymorphisms associated with CKD may differ among individuals with different lipid profiles. Stratification of subjects according to lipid profiles may thus be important for personalized prevention of CKD based on genetic information.