Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density

DeCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland.
Nature Genetics (Impact Factor: 29.65). 07/2009; 41(8):926-30. DOI: 10.1038/ng.404
Source: PubMed

ABSTRACT Kidney stone disease is a common condition. To search for sequence variants conferring risk of kidney stones, we conducted a genome-wide association study in 3,773 cases and 42,510 controls from Iceland and The Netherlands. We discovered common, synonymous variants in the CLDN14 gene that associate with kidney stones (OR = 1.25 and P = 4.0 x 10(-12) for rs219780[C]). Approximately 62% of the general population is homozygous for rs219780[C] and is estimated to have 1.64 times greater risk of developing the disease compared to noncarriers. The CLDN14 gene is expressed in the kidney and regulates paracellular permeability at epithelial tight junctions. The same variants were also found to associate with reduced bone mineral density at the hip (P = 0.00039) and spine (P = 0.0077).

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Available from: Gudmundur Bragi Walters, May 01, 2014
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    • "Recent genomewide association studies (GWASs) have identified several specific genes for BMD (e.g., WNT4- ZBTB40, C6orf97, TNFRSF11B-COLEC10, FABP3P2-TNFSF11) and calcaneus ultrasound parameters (i.e., WDR77) in European populations (Duncan et al., 2011; Richards et al., 2008; Rivadeneira et al., 2009; Roshandel et al., 2011; Styrkarsdottir et al., 2008; Styrkarsdottir et al., 2009; Thorleifsson et al., 2009; Xiong et al., 2009). "
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    • "(Curhan, et al, 1993, Siener, 2006) Known hereditary syndromes and recent population-based studies additionally support a genetic component to kidney stone disease. (Thorleifsson, et al, 2009) Men and individuals of white race seem to be at a higher risk for kidney stone disease than women and African Americans, respectively, (Stamatelou, et al, 2003, Gillen, et al, 2005b, Daudon, et al, 2006, Ramey, et al, 2004, Borghi, et al, 1999, Curhan, et al, 2005, Gillen, et al, 2005a, Hiatt, et al, 1982, Siener, et al, 2004, Soucie, et al, 1996) but many previous studies have focused on only one ethnic group or gender. "
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    • "Recently, a genome-wide association study (GWAS) showed that variants in claudin-14 (a gene expressed in the kidney that regulates paracellular permeability at epithelial tight junctions) were associated with kidney stones [19]. Inflammation may be one cause of urolithiasis [20]. "
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