A polymorphism of matrix Gla protein gene is associated with kidney stones.
OBJECTIVE
Matrix Gla protein, a potent calcification inhibitor in arterial vessels, is also expressed in the kidney and is up-regulated following the administration of ethylene glycol, a precursor of oxalate. Considering the analogous characteristics between arterial calcification and kidney stones, we identified variants of the human matrix Gla protein gene and investigated whether there is an association between MGP genetic polymorphisms and kidney stones.


METHODS
We studied single nucleotide polymorphisms in matrix Gla protein in 122 kidney stone cases and 125 controls. We resequenced the human genomic MGP gene, including the 1,000 bp promoter 5'-untranslated region, 4 exons and 3'-untranslated regions, and we performed systematic genetic analysis. A single nucleotide polymorphism was genotyped using a fluorescent 5'endonuclease assay and its association with kidney stones was analyzed.


RESULTS
We observed 19 polymorphisms. A single nucleotide polymorphism was associated with kidney stones (OR 0.51, 95% CI 0.30-0.87; p = 0.012). The G allele carrier had a 2-fold decreased kidney stone risk compared with A allele carriers in single nucleotide polymorphism 11 (OR 0.55, 95% CI 0.31-1.00, p = 0.047). We found no association between the polymorphism and kidney stone clinical characteristics.


CONCLUSIONS
Our findings show that an MGP gene polymorphism is associated with kidney stones and influences genetic susceptibility to kidney stones. In the future functional assays of the polymorphism should permit better understanding of the role of matrix Gla protein genetic variants and kidney stones.
Gao
Bing
B
Department of Nephro-urology, Nagoya City University Graduate School of Medical Sciences, 1 Kawasumi, Mizuho-ku, Nagoya 467-8601, Japan.
Yasui
Takahiro
T
Itoh
Yasunori
Y
Tozawa
Keiichi
K
Hayashi
Yutaro
Y
Kohri
Kenjiro
K
D000328:Adult; D000368:Aged; D002135:Calcium-Binding Proteins / Q000235:genetics*; D016022:Case-Control Studies; D016326:Extracellular Matrix Proteins / Q000235:genetics*; D005260:Female; D008040:Genetic Linkage / Q000235:genetics; D020022:Genetic Predisposition to Disease / Q000235:genetics; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D016133:Polymerase Chain Reaction; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D017422:Sequence Analysis, DNA; D000097568:Matrix Gla Protein
D002135:Calcium-Binding Proteins; D016326:Extracellular Matrix Proteins; D000097568:Matrix Gla Protein