Sequence variants in the CLDN14 gene associate with kidney stones and bone mineral density.
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).
Thorleifsson
Gudmar
G
DeCODE genetics, Sturlugata 8, 101 Reykjavik, Iceland. gudmar.thorleifsson@decode.is
Holm
Hilma
H
Edvardsson
Vidar
V
Walters
G Bragi
GB
Styrkarsdottir
Unnur
U
Gudbjartsson
Daniel F
DF
Sulem
Patrick
P
Halldorsson
Bjarni V
BV
de Vegt
Femmie
F
d'Ancona
Frank C H
FC
den Heijer
Martin
M
Franzson
Leifur
L
Christiansen
Claus
C
Alexandersen
Peter
P
Rafnar
Thorunn
T
Kristjansson
Kristleifur
K
Sigurdsson
Gunnar
G
Kiemeney
Lambertus A
LA
Bodvarsson
Magnus
M
Indridason
Olafur S
OS
Palsson
Runolfur
R
Kong
Augustine
A
Thorsteinsdottir
Unnur
U
Stefansson
Kari
K
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001483:Base Sequence; D015519:Bone Density / Q000235:genetics*; D002118:Calcium / Q000378:metabolism; D002891:Chromosomes, Human, Pair 21 / Q000235:genetics; D057167:Claudins; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics*; D008565:Membrane Proteins / Q000235:genetics*; D008875:Middle Aged; D008969:Molecular Sequence Data; D009154:Mutation / Q000235:genetics*
D057167:Claudins; D008565:Membrane Proteins; D002118:Calcium; C422064:claudin 14