The Uromodulin Gene Locus Shows Evidence of Pathogen Adaptation through Human Evolution.

Détails

ID Serval
serval:BIB_AE55B6A38786
Type
Article: article d'un périodique ou d'un magazine.
Collection
Publications
Institution
Titre
The Uromodulin Gene Locus Shows Evidence of Pathogen Adaptation through Human Evolution.
Périodique
Journal of the American Society of Nephrology : Jasn
Auteur⸱e⸱s
Ghirotto S., Tassi F., Barbujani G., Pattini L., Hayward C., Vollenweider P., Bochud M., Rampoldi L., Devuyst O.
ISSN
1046-6673 (Print)
ISSN-L
1046-6673
Statut éditorial
Publié
Date de publication
2016
Peer-reviewed
Oui
Volume
27
Numéro
10
Pages
2983-2996
Langue
anglais
Résumé
Common variants in the UMOD gene encoding uromodulin, associated with risk of hypertension and CKD in the general population, increase UMOD expression and urinary excretion of uromodulin, causing salt-sensitive hypertension and renal lesions. To determine the effect of selective pressure on variant frequency, we investigated the allelic frequency of the lead UMOD variant rs4293393 in 156 human populations, in eight ancient human genomes, and in primate genomes. The T allele of rs4293393, associated with CKD risk, has high frequency in most modern populations and was the one detected in primate genomes. In contrast, we identified only the derived, C allele in Denisovan and Neanderthal genomes. The distribution of the UMOD ancestral allele did not follow the ancestral susceptibility model observed for variants associated with salt-sensitive hypertension. Instead, the global frequencies of the UMOD alleles significantly correlated with pathogen diversity (bacteria, helminths) and prevalence of antibiotic-resistant urinary tract infections (UTIs). The inverse correlation found between urinary levels of uromodulin and markers of UTIs in the general population substantiates the link between UMOD variants and protection against UTIs. These data strongly suggest that the UMOD ancestral allele, driving higher urinary excretion of uromodulin, has been kept at a high frequency because of its protective effect against UTIs.
Pubmed
Web of science
Open Access
Oui
Création de la notice
17/03/2016 18:19
Dernière modification de la notice
20/08/2019 15:18
Données d'usage