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

• Published in: Gene Vol. 511; no. 2; pp. 127 - 130
• Main Authors: Lu, Xiuli, Gao, Bing, Liu, Zehui, Tian, Xiurong, Mao, Xu, Emmanuel, Newton, Zhu, Qiwen, Xiao, Chunling
• Format: Journal Article
• Language: English
• Published: Netherlands Elsevier B.V 15.12.2012
• Subjects: Aged; alleles; calcification; Calcium-Binding Proteins; Calcium-Binding Proteins - genetics; China; Ethnicity; Ethnicity - genetics; exons; extracellular matrix; Extracellular Matrix Proteins; Extracellular Matrix Proteins - genetics; Female; genetics; Humans; Kidney Calculi; Kidney Calculi - genetics; Kidney stone; kidneys; Male; Matrix Gla Protein; Middle Aged; odds ratio; polymerase chain reaction; Polymorphism, Single Nucleotide; renal calculi; risk; Single nucleotide polymorphism; China; COM; LR-PCR; OR; Matrix Gla protein; htSNP; CI; MGP; SNPs; LD; Single nucleotide polymorphism; Kidney stone
• ISSN: 0378-1119; 1879-0038; 1879-0038
• DOI: 10.1016/j.gene.2012.09.112

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. 728 subjects were recruited for the study. We firstly re-sequenced the human genomic MGP gene including the 1500bp 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. 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. 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. ► Polymorphisms of MGP gene were first investigated in the Chinese Han population. ► An SNP was found to be associated with kidney stone in the Chinese Han population. ► The association was confirmed in the Chinese and Japanese populations.