Association Analysis of 10 Candidate Genes Causing Mendelian Calcium Nephrolithiasis in the INCIPE Study: a South European General Population Cohort

Overview

Journal Clin Kidney J

Publisher Oxford University Press

Specialty Nephrology

Date 2023 Mar 3

PMID 36865011

Authors

Gloria Santoro

Gianmarco Lombardi

Stefano Andreola

Gian Luca Salvagno

Mirko Treccani

Elena Locatelli

Pietro Manuel Ferraro

Giuseppe Lippi

Giovanni Malerba

Giovanni Gambaro

Affiliations

Soon will be listed here.

Abstract

Background: Idiopathic calcium nephrolithiasis (ICN) is a common condition with a complex phenotype influenced by both environmental and genetic factors. In our study we investigated the association of allelic variants with the history of nephrolithiasis.

Methods: We genotyped and selected 10 candidate genes potentially related to ICN from 3046 subjects participating in the INCIPE survey cohort (Initiative on Nephropathy, of relevance to public health, which is Chronic, possibly in its Initial stages, and carries a Potential risk of major clinical End-points), a study enrolling subjects from the general population in the Veneto region in Italy.

Results: Overall, 66 224 variants mapping on the 10 candidate genes were studied. A total of 69 and 18 variants in INCIPE-1 and INCIPE-2, respectively, were significantly associated with stone history (SH). Only two variants, rs36106327 (chr20:54 171 755, intron variant) and rs35792925 (chr20:54 173 157, intron variant) of the gene were observed to be consistently associated with ICN. Neither variant has been previously reported in association with renal stones or other conditions. Carriers of variants showed a significant increase in the ratio of 1,25 (OH) vitamin D to 25 (OH) vitamin D compared with controls ( = .043). Although not associated with ICN in this study, the rs4811494 variant that was reported to be causative of nephrolithiasis was very prevalent in heterozygosity (20%).

Conclusion: Our data suggest a possible role for variants in the risk of nephrolithiasis. Genetic validation studies in larger sample sets will be necessary to confirm our findings.

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