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

• Published in: Nature Genetics
• Main Authors: Thorleifsson, Gudmar, Holm, Hilma, Edvardsson, Vidar, Walters, G Bragi, Styrkarsdottir, Unnur, Gudbjartsson, Daniel F, Sulem, Patrick, Halldorsson, Bjarni V, de Vegt, Femmie, d'Ancona, Frank C H, den Heijer, Martin, Franzson, Leifur, Christiansen, Claus, Alexandersen, Peter, Rafnar, Thorunn, Kristjansson, Kristleifur, Sigurdsson, Gunnar, Kiemeney, Lambertus A, Bodvarsson, Magnus, Indridason, Olafur S, Palsson, Runolfur, Kong, Augustine, Thorsteinsdottir, Unnur, Stefansson, Kari
• Other Authors: DeCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. [e-mail]
• Format: Article in Journal/Newspaper
• Language: English
• Published: Nature Pub. Co. 2009
• Subjects: Adult; Aged; 80 and over; Base Sequence; Bone Density; Calcium; Chromosomes; Human; Pair 21; Female; Genetic Predisposition to Disease; Humans; Kidney Calculi; Membrane Proteins; Middle Aged; Molecular Sequence Data; Mutation; Iceland
• Online Access: http://hdl.handle.net/2336/85798; https://doi.org/10.1038/ng.404

To access publisher full text version of this article. Please click on the hyperlink in Additional Links field 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).