Genetic contribution to renal function and electrolyte balance: a twin study

TLDR

The study aims to identify the heritability of key electrolytes to guide gene discovery and improve understanding of renal failure and hypertension. A classical twin study of 1,747 adult female pairs used intraclass correlations and maximum‑likelihood modeling to partition genetic and environmental contributions to serum and urinary electrolyte levels and creatinine clearance. Heritability estimates ranged from 27 % for serum magnesium to 63 % for creatinine clearance, with monozygotic twins showing higher correlations, indicating substantial genetic influence on electrolyte and renal function traits.

Abstract

A classical twin study was performed to assess the relative contributions of genetic and environmental factors to serum levels of calcium, phosphate and magnesium, urinary levels of calcium, sodium and potassium, and creatinine clearance. The subjects were 1747 adult female twin pairs: 539 monozygotic and 1208 dizygotic. The intraclass correlations were calculated, and maximum-likelihood model fitting was used to estimate genetic and environmental variance components. The intraclass correlations for all of the variables assessed were higher in monozygotic twin pairs. The heritabilities (with 95% confidence intervals) obtained from model fitting were: serum calcium, 33% (21–45%); serum phosphate, 58% (53–62%), serum magnesium, 27% (15–39%); 24h urinary potassium, 40% (27–51%); 24h urinary calcium, 52% (41–61%); 24h urinary sodium, 43% (30–54%); fractional excretion of sodium, 52% (44–59%); serum creatinine, 37% (25–49); calculated creatinine clearance, 63% (54–72%). This study provides evidence for the importance of genetic factors in determining urinary and blood levels of the major electrolytes involved in blood pressure regulation. Identifying heritability is the first step on the way to finding specific genes, which may improve our insight into the pathophysiology of the metabolism of these electrolytes, and thereby improve our understanding of the aetiology of complex diseases such as renal failure and hypertension.