ASN's Mission

ASN leads the fight to prevent, treat, and cure kidney diseases throughout the world by educating health professionals and scientists, advancing research and innovation, communicating new knowledge, and advocating for the highest quality care for patients.

learn more

Contact ASN

1401 H St, NW, Ste 900, Washington, DC 20005

email@asn-online.org

202-640-4660

The Latest on Twitter

Kidney Week

Abstract: FR-PO610

The Impact of TRPV-1 Genetic Polymorphisms on Serum Sodium Concentration in Elderly Patients

Session Information

Category: Fluid and Electrolytes

  • 901 Fluid and Electrolytes: Basic

Authors

  • Bais, Thomas, Academic Medical Center, Amsterdam, Netherlands
  • Tanck, Michael Wt, Academic Medical Center, Amsterdam, Netherlands
  • Richard, Edo, Academic Medical Center, Amsterdam, Netherlands
  • Van den born, Bert-jan, Academic Medical Center, Amsterdam, Netherlands
  • Vogt, Liffert, Academic Medical Center, Amsterdam, Netherlands
Background

Disorders of water balance, reflected as serum sodium concentration, are common in clinical practice but their pathophysiology remains incompletely understood. An N-terminal variant of transient receptor potential vanilloid-1 (delta N-TRPV-1) is important for mammalian central osmosensory transduction in hypothalamic magnocellular neurosecretory cells (MNCs) and is activated by hypertonicity, thus stimulating pituitary AVP secretion. Nevertheless, TRPV-1 single nucleotide polymorphisms (SNPs) have not yet been studied in relation to human osmoregulation.

Methods

We genotyped four common TRPV-1 SNPs in 507 acutely admitted elderly patients and 2480 ambulatory elderly patients, who were respectively at high- and low risk for hyponatremia. These SNPs include rs8065080 (I585V), rs224534 (T469I), rs222748 (H167H) and rs222749 (P91S). The effect of TRPV-1 SNPs on serum sodium concentration and the risk of hyponatremia was examined using multiple linear regression analysis and multiple logistic regression analysis. Haplotype analysis was employed to test the effect of combinations of TRPV-1 SNPs.

Results

In both cohorts, carriership of rs8065080, rs224534 and rs222748 did not significantly influence serum sodium concentrations. In acutely admitted elderly patients, univariate analysis demonstrated that serum sodium levels of rs222749 carriers were lower than of non-carriers, both in the entire cohort (133.9 ± 6.0 versus 135.7 ± 6.4 mmol/L, p=0.049) and in Western-European patients (133.7 ± 6.0 versus 135.7 ± 6.1 mmol/L, p=0.028). Acutely admitted patients rs222749 carriers were more likely to be included in the lowest sodium tertiles (serum Na <137 mmol/L; OR 2.54; 95% CI 1.18 - 5.34). In multiple linear regression analysis, carriership of the rs222749 allele was an independent predictor of serum sodium concentration in acutely admitted elderly patients but not in ambulatory patients.

Conclusion

In view of data from previous in vitro studies we hypothesize that rs222749 involves a gain-of-function mutation through enhanced delta N-TRPV-1 expression in MNCs, leading to increased pituitary AVP release and lower serum sodium levels in vulnerable patients.

Funding

  • Clinical Revenue Support