Modulation of aldosterone levels by aldosterone synthase promoter polymorphism and association with eGFR decline in patients with chronic kidney disease

Discov Med. 2018 Dec;26(145):251-260.

Abstract

To determine whether -344T/C CYP11B2 promoter polymorphism affects serum aldosterone levels and whether this polymorphism is an indicator of eGFR decline in patients with chronic kidney disease. -344 C/T CYP11B2 gene polymorphism analysis was performed in 96 adults with stages 1-5 CKD by using polymerase chain reaction. Serum aldosterone levels were measured at baseline and at 1.5-year follow-up. The primary outcome was the annual eGFR decline and the secondary outcome was the occurrence of cardio-cerebrovascular events. The genotype distribution of -344T/C SNP in the patients with CKD was: CC (9.4%), CT (53.1%), and TT (37.5%), nearly similar to the healthy non-CKD individuals as reported. Mean aldosterone levels were highest in the TT group and lowest in CC group (p = 0.036). Serum aldosterone level also showed a negative correlation with baseline eGFR in patients with eGFR >60 mL/min (r = -0.403, p < 0.001). The mean annual eGFR decline ratio was highest in the TT group and lowest in the CC group (p = 0.011). The incidence of cardio-cerebrovascular accidents was significantly higher in the TT group than in the CC and CT groups (p = 0.033). -344T/C promoter polymorphism of CYP11B2 modulated aldosterone levels in patients with all stages of CKD and was predictive of annual eGFR decline in CKD stages 3-4. In addition, the -344 T allele appeared to be an independent predictor of cardio-cerebrovascular events.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Adult
  • Aged
  • Aldosterone / metabolism*
  • Cardiovascular Diseases / etiology
  • Cardiovascular Diseases / genetics
  • Cardiovascular Diseases / physiopathology
  • Cerebrovascular Disorders / etiology
  • Cerebrovascular Disorders / genetics
  • Cerebrovascular Disorders / physiopathology
  • Cytochrome P-450 CYP11B2 / genetics*
  • Cytochrome P-450 CYP11B2 / metabolism
  • Disease Progression
  • Down-Regulation
  • Female
  • Follow-Up Studies
  • Glomerular Filtration Rate* / genetics
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Promoter Regions, Genetic*
  • Renal Insufficiency, Chronic* / complications
  • Renal Insufficiency, Chronic* / genetics
  • Renal Insufficiency, Chronic* / pathology
  • Renal Insufficiency, Chronic* / physiopathology

Substances

  • Aldosterone
  • Cytochrome P-450 CYP11B2