Abstract: FR-PO392
The Association between Kidney Function and Genetic Polymorphisms among Japanese Male Employees
Session Information
- CKD: Risk Factors for Incidence and Progression - I
November 03, 2017 | Location: Hall H, Morial Convention Center
Abstract Time: 10:00 AM - 10:00 AM
Category: Chronic Kidney Disease (Non-Dialysis)
- 301 CKD: Risk Factors for Incidence and Progression
Authors
- Imaizumi, Takahiro, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Kato, Sawako, Nagoya University Graduate School of Medicine, Nagoya, Japan
- Maruyama, Shoichi, Nagoya University Graduate School of Medicine, Nagoya, Japan
Background
Previous studies have implicated several single nucleotide polymorphisms (SNPs) in predisposition to chronic kidney disease (CKD). Though atherosclerotic disease is deeply involved in the incidence of CKD, whether SNPs related to arteriosclerosis are involved in CKD remains unclear. The purpose of this study was to identify SNPs that confer susceptibility to CKD and to examine whether the risk allele accumulation is associated with CKD.
Methods
We conducted a cross-sectional study using data of 4814 male workers which contained 432 participants with CKD to examine the association between eGFR and 59 candidate polymorphisms (17 CKD and 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).
Results
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, BMI, systolic blood pressure, and fasting blood glucose. Among these 8 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 (P = 0.061). However, adding GRS significantly improved IDI and cNRI (0.0057, P = 0.0028, and 0.212, P < 0.001, respectively).
Conclusion
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 with CKD.
Associated SNPs
| rs number | Near gene | Major/minor allele | Coefficient | 95% confidence interval | P value |
| rs3732379 | CX3CR1 | C/T | 1.25 | (0.004, 2.50) | 0.049 |
| rs17319721 | SHROOM3 | G/A | -1.16 | (-2.15, -0.16) | 0.023 |
| rs1800591 | MTP | G/T | 0.99 | (0.26, 1.72) | 0.0077 |
| rs4744712 | PIP5K1B | C/A | -0.75 | (-1.31, -0.19) | 0.0088 |
| rs662799 | APOA5 | A/G | -0.61 | (-1.18, -0.046) | 0.034 |
| rs3782886 | BRAP | A/G | -1.63 | (-2.25, -1.02) | <0.0001 |
| rs2467853 | SPATA5L1 | G/T | 2.07 | (0.89, 3.24) | 0.0006 |
| rs1024611 | MCP1 | C/T | -0.65 | (-1.22, -0.084) | 0.025 |
Funding
- Commercial Support – Toyota motor corporation