GENETIC ASSOCIATION BETWEEN HYPERNATREMIA AND THE IMPAIRED KIDNEY FUNCTION IN GENERAL POPULATION

Abstract

Introduction and Aims: Hypernatremia is one of most common electrolyte problems and its point prevalence is progressively increased in patients with advanced chronic kidney disease, but the role of genetic mechanism in this association remains to be determined. We performed genome-wide association study (GWAS) to find susceptible single-nucleotide polymorphisms (SNPs) for increased serum sodium concentration in general population and possible SNP(s) may be associated with impaired kidney function.

Methods: We analyzed anthropometric, biochemical, and genetic data from a community-based study. Hypernatremia was defined as sodium concentration (Na+, mEq/L) of 145 or more. Eligible as cases were all native Koreans without significant medical illness and a total 5604 participants were divided in into control (n = 4501) and hypernatremic (n = 1103) according to their serum levels.

Results: Multiple linear regression analysis showed that there was reverse relationship between serum sodium concentration and estimated glomerular filtration rate (eGFR, β = -0.6129, r2 = 0.4972, p < 0.0001). Subsequent GWAS revealed that a susceptibility locus at the FAM49A gene (encoding FAM49A) in 2p24.2 was associated with hypernatremia. Multiple logistic analysis showed that genetic polymorphism at rs11676612 in the FAM49A gene had dominant genetic effect on declined eGFR and further adjustment for age, gender, systolic blood pressure, waist circumference, albumin, and serum triglyceride level did not attenuate this association (OR = 1.753, 95% CI = 1.062-2.893).

Conclusions: Our results suggest that genetic polymorphism in the FAM49A gene is associated with susceptibility to impaired kidney function in subject with hypernatremia. Further study is needed to explore the details of the physiological and molecular mechanisms underlying this association.