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Abstract: PO1041

Energy Homeostasis Gene Polymorphisms and Survival of Hemodialysis Patients

Session Information

Category: Dialysis

  • 701 Dialysis: Hemodialysis and Frequent Dialysis

Authors

  • Swiderska, Monika K., Uniwersytet Medyczny imienia Karola Marcinkowskiego w Poznaniu, Poznan, Wielkopolskie, Poland
  • Mostowska, Adrianna, Uniwersytet Medyczny imienia Karola Marcinkowskiego w Poznaniu, Poznan, Wielkopolskie, Poland
  • Jagodzinski, Pawel P., Uniwersytet Medyczny imienia Karola Marcinkowskiego w Poznaniu, Poznan, Wielkopolskie, Poland
  • Grzegorzewska, Alicja E., Uniwersytet Medyczny imienia Karola Marcinkowskiego w Poznaniu, Poznan, Wielkopolskie, Poland
Background

Patients who undergo hemodialysis (HD) therapy have an increased risk of death compared to the general population. Single nucleotide variants (SNVs) of energy homeostasis influence the susceptibility to diabetes mellitus (DM), dyslipidemia, and coronary artery disease (CAD). We investigated whether selected SNVs related to energy homeostasis are associated with mortality risk in HD patients.

Methods

The study included 471 HD patients who were tested for 11 SNVs in FOXO3, IGFBP3, FABP1, PCSK9, ANGPLT6, and ANGPLT8 genes using HRM analysis and TaqMan assays. FOXO3, IGFBP3, L-FABP, PCSK9, ANGPLT6, and ANGPLT8 plasma concentrations were measured by ELISA in 71 HD patients. The Kaplan-Meier method and Cox proportional hazard models were used for survival analyses.

Results

Patients with ANGPLT8 rs737337 CC genotype had over 3-fold increased risk of death compared with the carriers of the major allele (log-rank test p=0.002; HR 3.4; 95%CI 1.5–7.7;p=0.003). rs737337 CC genotype was in particular a risk factor for cardiac (2e-4; 5.5; 2–15.1; 8E-4) and cardiovascular deaths (0.004; 4; 1.5–10.7; 0.007). The associations mentioned above remained significant after adjustment for gender, DM, CAD, age at RRT onset, BMI and CRP (p=0.03, 0.004 and 0.02 for overall survival, cardiac and cardiovascular deaths, respectively). ANGPLT8 rs737337 was also associated with an increased risk of diabetic nephropathy (OR 1.8;95%CI 1.1–2.9; p=0.02). Plasma ANGPLT8 levels were increased in patients diagnosed with CAD (p=0.028). Bearers of IGFBP3 rs3110697 variant A allele had increased risk of cardiovascular mortality (HR 1.3; 95%CI 1–1.6; p=0.02, adjusted p=NS). IGFBP3 rs3110697 positively correlated with the diagnosis of CAD (p=0.006), myocardial infarct (p=0.01) and dyslipidemia (p=0.02) as well as with CRP concentrations (p=0.005). Carriers of FOXO3 rs4946936 CT genotype had increased risk of cardiac death (HR 1.6; 95% CI 1.1–2.4; p=0.03, adjusted p=NS), whereas FOXO3 rs2802292 TT genotype was associated with decreased risk of vascular mortality (HR 0.4; 95%CI 0.2–0.8; p=0.005). The association remained significant after adjustment (p=0.002). The analyzed proteins did not correlate with the survival probability of HD patients.

Conclusion

ANGPLT8 rs737337, IGFBP3 rs3110697, FOXO3 rs2802292, and rs4946936 are prognostic factors of survival among HD patients.

Funding

  • Government Support - Non-U.S.