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

Abstract

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.

DNA hypermethylation and DNA hypomethylation is present at different loci in chronic kidney disease

“…55,56 PTPRN2 is an autoantigen associated with type 1 diabetes mellitus 57,58 and variation in the PTPRN2 gene has been associated with CKD in Japanese individuals with hypertension and diabetes mellitus. 59 SNP rs13243294 in this gene may affect the methylation of cg26059287, but genotypes at this position did not account for the significant difference in methylation in a UK population.…”

Analysis of the association of an MMP1 promoter polymorphism and transcript levels with chronic periodontitis and end-stage renal disease in a Brazilian population

“…It was observed in Japanese subjects that the MMP1-1607*1G allele was significantly associated with CKD 53 and with CKD in individuals with a low serum concentration of HDL-cholesterol. 54 Interestingly, with regard to periodontal indices, we found that the MMP1*1G was associated with PI in groups without CKD. Based on the presence of both periodontal bacteria and interleukins (e.g., IL-1, IL-6), which regulate MMP-1 expression, an association of the MMP1*2G allele with higher means of PI might be expected; however, dental biofilm represents a more favourable environment for the initiation rather than the progression of CP.…”

Association of gene polymorphisms with chronic kidney disease in Japanese individuals

“…Given that atherosclerosis is an important risk factor for CKD (15), genetic variants related to atherosclerotic disease such as ischemic stroke and myocardial infarction might also contribute to the development of CKD. We have not examined the relation of these polymorphisms in the previous studies (7,8,(16)(17)(18)(19).…”

“…Although genetic linkage analyses (5) and association studies (6)(7)(8)(9)(10) have implicated several loci and candidate genes in predisposition to CKD, the genes that confer susceptibility to this condition remain to be identified definitively. In addition, given the ethnic differences in lifestyle and environmental factors as well as in genetic background and renal function, it is important to examine genetic variants related to CKD in each ethnic group.…”