Association between kidney function and genetic polymorphisms in atherosclerotic and chronic kidney diseases: A cross-sectional study in Japanese male workers

PLoS One. 2017 Oct 10;12(10):e0185476. doi: 10.1371/journal.pone.0185476. eCollection 2017.

Abstract

Background: Several single nucleotide polymorphisms (SNPs) have been implicated in the predisposition to chronic kidney disease (CKD). Atherosclerotic disease is deeply involved in the incidence of CKD; however, whether SNPs related to arteriosclerosis are involved in CKD remains unclear. This study aimed to identify SNPs associated with CKD and to examine whether risk allele accumulation is associated with CKD.

Methods: We conducted a cross-sectional study using data of 4814 male workers to examine the association between estimated glomerular filtration rate (eGFR) and 59 candidate polymorphisms (17 CKD, 42 atherosclerotic diseases). We defined the genetic risk score (GRS) as the total number of risk alleles that showed a significant association in this analysis and examined the relationship with CKD (eGFR < 60 ml/min/1.73m2). Multivariate logistic regression, discrimination by area under the receiver operating characteristic curve, integrated discrimination improvement (IDI), and category-free net reclassification improvement (cNRI) were evaluated.

Results: In total, 432 participants were categorized as having CKD. We found eight candidate SNPs with P value < 0.05 (CX3CR1 rs3732379, SHROOM3 rs17319721, MTP rs1800591, PIP5K1B rs4744712, APOA5 rs662799, BRAP rs3782886, SPATA5L1 rs2467853, and MCP1 rs1024611) in the multivariate linear regression adjusted for age, body mass index, systolic blood pressure, and fasting blood glucose. Among these eight SNPs, BRAP rs3782886 and SPATA5L1 rs2467853 were significantly associated with eGFR (false discovery rate < 0.05). GRS was significantly associated with CKD (odds ratio, 1.17; 95% confidence interval, 1.09-1.26). C-statisics improved from 0.775 to 0.780 but showed no statistical significance. However, adding GRS significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001, respectively).

Conclusions: After adjustment for clinical factors, kidney function was associated with BRAP rs3782886 and SPATA5L1 rs2467853 and the GRS for CKD that we developed was associated CKD.

MeSH terms

  • Adult
  • Alleles
  • Asian People
  • Atherosclerosis / epidemiology
  • Atherosclerosis / genetics*
  • Atherosclerosis / pathology
  • Genetic Association Studies
  • Genetic Predisposition to Disease*
  • Genotype
  • Humans
  • Japan / epidemiology
  • Kidney / pathology
  • Kidney Failure, Chronic / epidemiology
  • Kidney Failure, Chronic / genetics*
  • Kidney Failure, Chronic / pathology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Renal Insufficiency, Chronic / epidemiology
  • Renal Insufficiency, Chronic / genetics*
  • Renal Insufficiency, Chronic / pathology
  • Risk Factors

Grants and funding

Support for this work was provided by the Center of Innovation Stream Program at the Nagoya University Institute of Innovation for Future Society, government-led Comprehensive Special Zones for Local Revitalization project, and Toyota Motor Corporation Limited. Five authors (Masamitsu Iwata, Toru Nakashima, Hiroshi Yasui, Hideki Takamatsu, and Hiroshi Okajima) have an affiliation to the commercial funders of this research study: Toyota Motor Corporation Limited. We carefully reviewed the contribution of these authors and confirmed that although the funder provided support in the form of salaries for the five authors, it did not have any additional role in the study design, data collection and analysis, decision to publish, or preparation of the manuscript.