PURPOSE - Solute carrier family 26 member 6 (SLC26A6) is a multifunctional anion transporter, and plays a critical physiological role in the transport of oxalate anions. Recognizing genetic variant of SLC26A6 will advance our understanding of oxalate transport in the formation of calcium oxalate stone.
MATERIALS AND METHODS - All non-synonymous SNPs (nsSNPs) reported in human SLC26A6 were investigated using four different in silico tools including SIFT, PROVEAN, PhD-SNP and MutPred. 426 subjects including 225 kidney stone cases and 201 healthy controls were collected for genotyping the candidate disease-associated nsSNP using an allele-specific PCR. Furthermore, the structural consequences due to the mutation were assessed using homology modeling and molecular dynamics simulation methods RESULTS: A nsSNP (rs184187143) was identified more probable disease-associated variant in SLC26A6 gene by in silico screening. The C allele carrier had a 6. 1-fold increased kidney stone risk compared with G allele carriers in the nsSNP (OR=6. 1; 95%CI, 1. 36-27. 38; p=0. 007). The mutation from arginine to glycine leads to loss of two hydrogen bonds and unstable structure in STAS domain of SLC26A6.
CONCLUSIONS - Our results indicate that the variant (G539R) in the SLC26A6 gene is associated with kidney stone risk, and provide a clear clue for further achieving insight into oxalate transport in the kidney stone formation.
The Journal of urology. 2016 Jan 23 [Epub ahead of print]
Xiuli Lu, Deliang Sun, Bo Xu, Jichuan Pan, Yanhong Wei, Xu Mao, Daojun Yu, Hongsheng Liu, Bing Gao
Department of Biochemistry and Cell Biology, School of Life Science, Liaoning University, Shenyang, China; Research Center for Computer Simulating and Information Processing of Bio-macromolecules of Liaoning Province, Shenyang, China. , Department of Biochemistry and Cell Biology, School of Life Science, Liaoning University, Shenyang, China. , Department of Biochemistry and Cell Biology, School of Life Science, Liaoning University, Shenyang, China. , Department of cell biology and genetics, Shenyang Medical College, 146 Huanghe North Street, Shenyang 110034, China. , Department of cell biology and genetics, Shenyang Medical College, 146 Huanghe North Street, Shenyang 110034, China. , Department of cell biology and genetics, Shenyang Medical College, 146 Huanghe North Street, Shenyang 110034, China. , Department of cell biology and genetics, Shenyang Medical College, 146 Huanghe North Street, Shenyang 110034, China. , Research Center for Computer Simulating and Information Processing of Bio-macromolecules of Liaoning Province, Shenyang, China. , Department of cell biology and genetics, Shenyang Medical College, 146 Huanghe North Street, Shenyang 110034, China; Key Laboratory of Environment and Population Health of Liaoning Education Ministry, Shenyang Medical College, 146 Huanghe North Street, Shenyang 110034, China; China-Japan Kidney Stone Research Center, 146 Huanghe North Street, Shenyang 110034, China.