Evidence for epistatic interaction between VDR and SLC13A2 genes in the pathogenesis of hypocitraturia in recurrent calcium oxalate stone formers

Domenico Rendina, Gianpaolo De Filippo, Fernando Gianfrancesco, Riccardo Muscariello, Michele Schiano di Cola, Pasquale Strazzullo, Teresa Esposito

Research output: Contribution to journalArticle

4 Citations (Scopus)

Abstract

BACKGROUND: Genetic factors play a key role in the pathogenesis of hypocitraturia, a common risk factor for nephrolithiasis. The Na(+)-dicarboxylate cotransporter NaDC1, encoded by the sodium-dicarboxylate cotransporter (SLC13A2) gene, is a major determinant of urinary citrate excretion and its biological functions are regulated also by the vitamin D/Vitamin D receptor (VDR) biological system. The aim of this case-control study was to evaluate the possible epistatic interaction between VDR (rs731236)and SLC13A2 (rs11567842) allelic variants in the pathogenesis of hypocitraturia.

METHODS: Recurrent calcium-oxalate stone formers (SF) with or without hypocitraturia and healthy controls (C) were genotyped. Gene-gene interactions were estimated by the 1.0 software package of multifactor dimensionality reduction (MDR).

RESULTS: The prevalence of VDR (TT) and SLC13A2 (GG) genotypes was higher in hypocitraturic SF compared to C (odds ratio [OR] 3.24, 95 % confidence interval [CI] 1.38-7.60 for VDR (TT) vs. VDR (tt) and OR 4.06, 95 % CI 1.75-9.42 for SLC13A2 (GG) vs. SLC13A2 (AA) ). MDR analysis indicated a significant interaction between VDR (TT) and SLC13A2 (GG) in hypocitraturic SF compared to C [OR 3.81 (2.11-6.88)]. These data are compatible with an epistatic interaction between the VDR (TT) and SLC13A2 (GG) genotypes with a significant impact on the magnitude of the effect (suppressive effect).

CONCLUSIONS: These results point to an epistatic interaction between the VDR and the SLC13A2 alleles in the pathogenesis of idiopathic hypocitraturia in calcium-oxalate SF.

Original languageEnglish
JournalJournal of Nephrology
DOIs
Publication statusPublished - Jun 2017

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Calcium Oxalate
Calcitriol Receptors
Genes
Multifactor Dimensionality Reduction
Odds Ratio
Genotype
Confidence Intervals
Nephrolithiasis
Vitamin D
Citric Acid
Case-Control Studies
Software
Sodium
Alleles

Keywords

  • Journal Article

Cite this

Evidence for epistatic interaction between VDR and SLC13A2 genes in the pathogenesis of hypocitraturia in recurrent calcium oxalate stone formers. / Rendina, Domenico; De Filippo, Gianpaolo; Gianfrancesco, Fernando; Muscariello, Riccardo; Schiano di Cola, Michele; Strazzullo, Pasquale; Esposito, Teresa.

In: Journal of Nephrology, 06.2017.

Research output: Contribution to journalArticle

Rendina, Domenico ; De Filippo, Gianpaolo ; Gianfrancesco, Fernando ; Muscariello, Riccardo ; Schiano di Cola, Michele ; Strazzullo, Pasquale ; Esposito, Teresa. / Evidence for epistatic interaction between VDR and SLC13A2 genes in the pathogenesis of hypocitraturia in recurrent calcium oxalate stone formers. In: Journal of Nephrology. 2017.
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title = "Evidence for epistatic interaction between VDR and SLC13A2 genes in the pathogenesis of hypocitraturia in recurrent calcium oxalate stone formers",
abstract = "BACKGROUND: Genetic factors play a key role in the pathogenesis of hypocitraturia, a common risk factor for nephrolithiasis. The Na(+)-dicarboxylate cotransporter NaDC1, encoded by the sodium-dicarboxylate cotransporter (SLC13A2) gene, is a major determinant of urinary citrate excretion and its biological functions are regulated also by the vitamin D/Vitamin D receptor (VDR) biological system. The aim of this case-control study was to evaluate the possible epistatic interaction between VDR (rs731236)and SLC13A2 (rs11567842) allelic variants in the pathogenesis of hypocitraturia.METHODS: Recurrent calcium-oxalate stone formers (SF) with or without hypocitraturia and healthy controls (C) were genotyped. Gene-gene interactions were estimated by the 1.0 software package of multifactor dimensionality reduction (MDR).RESULTS: The prevalence of VDR (TT) and SLC13A2 (GG) genotypes was higher in hypocitraturic SF compared to C (odds ratio [OR] 3.24, 95 {\%} confidence interval [CI] 1.38-7.60 for VDR (TT) vs. VDR (tt) and OR 4.06, 95 {\%} CI 1.75-9.42 for SLC13A2 (GG) vs. SLC13A2 (AA) ). MDR analysis indicated a significant interaction between VDR (TT) and SLC13A2 (GG) in hypocitraturic SF compared to C [OR 3.81 (2.11-6.88)]. These data are compatible with an epistatic interaction between the VDR (TT) and SLC13A2 (GG) genotypes with a significant impact on the magnitude of the effect (suppressive effect).CONCLUSIONS: These results point to an epistatic interaction between the VDR and the SLC13A2 alleles in the pathogenesis of idiopathic hypocitraturia in calcium-oxalate SF.",
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author = "Domenico Rendina and {De Filippo}, Gianpaolo and Fernando Gianfrancesco and Riccardo Muscariello and {Schiano di Cola}, Michele and Pasquale Strazzullo and Teresa Esposito",
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TY - JOUR

T1 - Evidence for epistatic interaction between VDR and SLC13A2 genes in the pathogenesis of hypocitraturia in recurrent calcium oxalate stone formers

AU - Rendina, Domenico

AU - De Filippo, Gianpaolo

AU - Gianfrancesco, Fernando

AU - Muscariello, Riccardo

AU - Schiano di Cola, Michele

AU - Strazzullo, Pasquale

AU - Esposito, Teresa

PY - 2017/6

Y1 - 2017/6

N2 - BACKGROUND: Genetic factors play a key role in the pathogenesis of hypocitraturia, a common risk factor for nephrolithiasis. The Na(+)-dicarboxylate cotransporter NaDC1, encoded by the sodium-dicarboxylate cotransporter (SLC13A2) gene, is a major determinant of urinary citrate excretion and its biological functions are regulated also by the vitamin D/Vitamin D receptor (VDR) biological system. The aim of this case-control study was to evaluate the possible epistatic interaction between VDR (rs731236)and SLC13A2 (rs11567842) allelic variants in the pathogenesis of hypocitraturia.METHODS: Recurrent calcium-oxalate stone formers (SF) with or without hypocitraturia and healthy controls (C) were genotyped. Gene-gene interactions were estimated by the 1.0 software package of multifactor dimensionality reduction (MDR).RESULTS: The prevalence of VDR (TT) and SLC13A2 (GG) genotypes was higher in hypocitraturic SF compared to C (odds ratio [OR] 3.24, 95 % confidence interval [CI] 1.38-7.60 for VDR (TT) vs. VDR (tt) and OR 4.06, 95 % CI 1.75-9.42 for SLC13A2 (GG) vs. SLC13A2 (AA) ). MDR analysis indicated a significant interaction between VDR (TT) and SLC13A2 (GG) in hypocitraturic SF compared to C [OR 3.81 (2.11-6.88)]. These data are compatible with an epistatic interaction between the VDR (TT) and SLC13A2 (GG) genotypes with a significant impact on the magnitude of the effect (suppressive effect).CONCLUSIONS: These results point to an epistatic interaction between the VDR and the SLC13A2 alleles in the pathogenesis of idiopathic hypocitraturia in calcium-oxalate SF.

AB - BACKGROUND: Genetic factors play a key role in the pathogenesis of hypocitraturia, a common risk factor for nephrolithiasis. The Na(+)-dicarboxylate cotransporter NaDC1, encoded by the sodium-dicarboxylate cotransporter (SLC13A2) gene, is a major determinant of urinary citrate excretion and its biological functions are regulated also by the vitamin D/Vitamin D receptor (VDR) biological system. The aim of this case-control study was to evaluate the possible epistatic interaction between VDR (rs731236)and SLC13A2 (rs11567842) allelic variants in the pathogenesis of hypocitraturia.METHODS: Recurrent calcium-oxalate stone formers (SF) with or without hypocitraturia and healthy controls (C) were genotyped. Gene-gene interactions were estimated by the 1.0 software package of multifactor dimensionality reduction (MDR).RESULTS: The prevalence of VDR (TT) and SLC13A2 (GG) genotypes was higher in hypocitraturic SF compared to C (odds ratio [OR] 3.24, 95 % confidence interval [CI] 1.38-7.60 for VDR (TT) vs. VDR (tt) and OR 4.06, 95 % CI 1.75-9.42 for SLC13A2 (GG) vs. SLC13A2 (AA) ). MDR analysis indicated a significant interaction between VDR (TT) and SLC13A2 (GG) in hypocitraturic SF compared to C [OR 3.81 (2.11-6.88)]. These data are compatible with an epistatic interaction between the VDR (TT) and SLC13A2 (GG) genotypes with a significant impact on the magnitude of the effect (suppressive effect).CONCLUSIONS: These results point to an epistatic interaction between the VDR and the SLC13A2 alleles in the pathogenesis of idiopathic hypocitraturia in calcium-oxalate SF.

KW - Journal Article

U2 - 10.1007/s40620-016-0348-8

DO - 10.1007/s40620-016-0348-8

M3 - Article

C2 - 27639591

JO - Journal of Nephrology

JF - Journal of Nephrology

SN - 1121-8428

ER -