New gene linked to kidney function identified

Generation Scotland volunteer data used in large scale study that identifies a new gene location affecting kidney function.

Uromodulin image

Uromodulin is the most common protein found in normal urine.  It plays lots of key roles in kidney physiology and disease. For example, many people who develop uromodulin-linked kidney disease are more likely to have high levels of uric acid in the blood- which is normally removed from the body in urine. There is still a lot to learn about the mechanisms that look after urine release.

In a recent international study,  researchers aimed to understand these mechanisms in more detail. They decided to combine and study the results of many different research projects. They focused their efforts on genome-wide association studies - a research method used to link genetic variations with particular health conditions. They specifically looked at studies including uromodulin volunteer data. The data was examined across 29,512 volunteers with European ancestry from 13 projects, including 7,652 Generation Scotland volunteers.

Their research identified two genome-wide significant signals. Firstly, a gene location was discovered in the KRT40 gene, which codes for the protein keratin-40. Keratin is the protein that makes up your hair and nails but can also be found in the kidney, such as keratin-40.  Secondly, two independent sets of genetic variations were found that were already known before. 

The researchers then tested the distribution of these genes in sections of the kidney. They looked at the effects of keratin-40 on uromodulin processing through fluorescence microscopy. The researchers found an overlap of where keratin-40 is located with where uromodulin is found. By the same method, Keratin-40 was shown to influence uromodulin expression in certain kidney cells and to have impacted uromodulin processing and excretion.

These results give new insights into the biology of uromodulin and the role of keratins in the kidney. The researchers hope this new knowledge will lead to better future treatments for health conditions affecting the kidneys.

This paper was published in the Journal of The American Society of Nephrology and can be found in the link below.

Meta-GWAS Reveals Novel Genetic Variants Associated with Urinary Excretion of Uromodulin