A polymorphism of matrix Gla protein gene is associated with kidney stone in the Chinese Han population.

PURPOSE: Matrix Gla protein (MGP) is a molecular determinant regulating the extracellular matrix calcification. To further confirm whether the MGP genetic polymorphism was universally associated with the risk of kidney stone, we investigated the association of genetic polymorphisms of MGP with kidney stone in the Chinese Han population. MATERIALS AND METHODS: 728 subjects were recruited for the study. We firstly re-sequenced the human genomic MGP gene including the 1500 bp promoter, 5'-UTR, 4 exons and 3'-untranslated regions, identified single nucleotide polymorphisms (SNPs) in MGP, and performed an association analysis with kidney stones in 54 subjects of the Chinese Han population. A candidate tag SNP was genotyped in total subjects using an allele specific PCR, and further analyzed the association with kidney stone. RESULTS: We identified 18 polymorphisms including four tag SNPs. A tag SNPrs4236 was associated with kidney stones. The G allele carrier had a 1.373-fold reduced kidney stone risk compared with A allele carriers in SNPrs4236 (odds ratios (OR)=1.373; 95%CI, 1.051-1.793; p=0.019). However, we did not find an association between the polymorphism and clinical characteristics of kidney stones. CONCLUSIONS: Our findings showed that SNPrs4236 of the MGP gene is associated with kidney stones in the Chinese Han population, and influences the genetic susceptibility to kidney stones. In the future, functional assays of the polymorphism should permit a better understanding of the role of MGP genetic variants and kidney stones.

Renal tubular epithelial cell injury, apoptosis and inflammation are involved in melamine-related kidney stone formation.

The objective of this study is to understand pathogenesis of melamine-related kidney stone formation. We investigated the characterization of renal tubular cell under exposure to a mixture of melamine and cyanuric acid in vivo. Male Sprague-Dawley rats were separated into two experimental groups. Treatment group was administered daily with a standard commercial diet mixing with melamine and cyanuric acid, and control group was given a normal diet. Rat kidney specimens were stained with hematoxylin/eosin and the crystals were examined using a polarizing microscope. Renal tubular epithelial cells were observed by transmission electron microscopy. Semiquantitative RT-PCR assay was performed to determine monocyte chemoattractant protein-1 (MCP-1) mRNA expression, a protein in response to various proinflammatory stimuli. Apoptotic cells were examined by TUNEL assay. Melamine-associated crystals formed in glomerulus and wide renal tubule segment including proximal convoluted renal tubules, distal convoluted renal tubules, the limb loops of Henle and medullary collecting ducts in the cortex and medulla. Light microscopy results showed that the crystals lead to tubular lumen dilatation and tubular epithelial cell necrosis. It was observed that nucleus of renal tubular epithelial cells became irregular outlines and condensed, lysosomal-related structures increased, and integrity of renal tubule was deficient under electron microscopy. Apoptotic cells were noted widely in cortex and medulla. MCP-1 mRNA expression was significantly increased in the melamine and cyanuric acid-administrated group. Renal tubular epithelial cell injury, apoptosis and inflammation are involved in melamine-related kidney stone formation. Our findings are important for understanding pathogenesis of melamine-related kidney stone formation and estimating its clinical prognosis.