title: In Silico Screening and Molecular Dynamic Study of Nonsynonymous Single Nucleotide Polymorphisms Associated with Kidney Stones in the SLC26A6 Gene.
abstract: SLC26A6 is a multifunctional anion transporter with a critical physiological role in the transport of oxalate anions. Recognizing a genetic variant of SLC26A6 would advance our understanding of oxalate transport in the formation of calcium oxalate stones.
  
  
  
  All nsSNPs (nonsynonymous single nucleotide polymorphisms) reported in human SLC26A6 were investigated using 4 in silico tools, including SIFT (Sorting Intolerant From Tolerant), PROVEAN (Protein Variation Effect Analyzer), PhD-SNP (Predictor of human Deleterious Single Nucleotide Polymorphisms) and MutPred. A total of 426 subjects, including 225 with kidney stones and 201 healthy controls, were included in study to genotype the candidate disease associated nsSNP using allele specific polymerase chain reaction. Furthermore, the structural consequences due to the mutation were assessed using homology modeling and molecular dynamics simulation methods.
  
  
  
  The nsSNP rs184187143 was identified as a more probable disease associated variant in the SLC26A6 gene by in silico screening. The C allele carrier showed 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). We found that the mutation from arginine to glycine leads to the loss of 2 hydrogen bonds and to an unstable structure in the STAS domain of SLC26A6.
  
  
  
  Our results indicate that the variant G539R in the SLC26A6 gene is associated with kidney stone risk, providing a clear clue to further achieve insight into oxalate transport in kidney stone formation.
authors.affiliation: Department of Biochemistry and Cell Biology, School of Life Science, Liaoning University, Shenyang, People's Republic of China; Research Center for Computer Simulating and Information Processing of Bio-macromolecules of Liaoning Province, Shenyang, People's Republic of China.
authors.forename: Xiuli
authors.initials: X
authors.lastname: Lu
authors.affiliation: Department of Biochemistry and Cell Biology, School of Life Science, Liaoning University, Shenyang, People's Republic of China.
authors.forename: Deliang
authors.initials: D
authors.lastname: Sun
authors.affiliation: Department of Biochemistry and Cell Biology, School of Life Science, Liaoning University, Shenyang, People's Republic of China.
authors.forename: Bo
authors.initials: B
authors.lastname: Xu
authors.affiliation: Department of Cell Biology and Genetics, Shenyang Medical College, Shenyang, People's Republic of China.
authors.forename: Jichuan
authors.initials: J
authors.lastname: Pan
authors.affiliation: Department of Cell Biology and Genetics, Shenyang Medical College, Shenyang, People's Republic of China.
authors.forename: Yanhong
authors.initials: Y
authors.lastname: Wei
authors.affiliation: Department of Cell Biology and Genetics, Shenyang Medical College, Shenyang, People's Republic of China.
authors.forename: Xu
authors.initials: X
authors.lastname: Mao
authors.affiliation: Department of Cell Biology and Genetics, Shenyang Medical College, Shenyang, People's Republic of China.
authors.forename: Daojun
authors.initials: D
authors.lastname: Yu
authors.affiliation: Research Center for Computer Simulating and Information Processing of Bio-macromolecules of Liaoning Province, Shenyang, People's Republic of China.
authors.forename: Hongsheng
authors.initials: H
authors.lastname: Liu
authors.affiliation: Department of Cell Biology and Genetics, Shenyang Medical College, Shenyang, People's Republic of China; Key Laboratory of Environment and Population Health of Liaoning Education Ministry, Shenyang Medical College, Shenyang, People's Republic of China; China-Japan Kidney Stone Research Center, Shenyang, People's Republic of China. Electronic address: gaobingdr@hotmail.com.
authors.forename: Bing
authors.initials: B
authors.lastname: Gao
mesh_terms: D000328:Adult; D000368:Aged; D016022:Case-Control Studies; D016208:Databases, Factual; D005260:Female; D005819:Genetic Markers; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics*; D008297:Male; D026901:Membrane Transport Proteins / Q000235:genetics*; D008875:Middle Aged; D056004:Molecular Dynamics Simulation; D009154:Mutation; D020641:Polymorphism, Single Nucleotide; D000076988:Sulfate Transporters
chemical_list: D005819:Genetic Markers; D026901:Membrane Transport Proteins; C439529:SLC26A6 protein, human; D000076988:Sulfate Transporters
keywords: SLC26A6 protein, human; computer simulation; kidney calculi; oxalates; polymorphism, single nucleotide