title: A whole genome SNP genotyping by DNA microarray and candidate gene association study for kidney stone disease.
abstract: BACKGROUND
  Kidney stone disease (KSD) is a complex disorder with unknown etiology in majority of the patients. Genetic and environmental factors may cause the disease. In the present study, we used DNA microarray to genotype single nucleotide polymorphisms (SNP) and performed candidate gene association analysis to determine genetic variations associated with the disease.
  
  
  METHODS
  A whole genome SNP genotyping by DNA microarray was initially conducted in 101 patients and 105 control subjects. A set of 104 candidate genes reported to be involved in KSD, gathered from public databases and candidate gene association study databases, were evaluated for their variations associated with KSD.
  
  
  RESULTS
  Altogether 82 SNPs distributed within 22 candidate gene regions showed significant differences in SNP allele frequencies between the patient and control groups (P < 0.05). Of these, 4 genes including BGLAP, AHSG, CD44, and HAO1, encoding osteocalcin, fetuin-A, CD44-molecule and glycolate oxidase 1, respectively, were further assessed for their associations with the disease because they carried high proportion of SNPs with statistical differences of allele frequencies between the patient and control groups within the gene. The total of 26 SNPs showed significant differences of allele frequencies between the patient and control groups and haplotypes associated with disease risk were identified. The SNP rs759330 located 144 bp downstream of BGLAP where it is a predicted microRNA binding site at 3'UTR of PAQR6 - a gene encoding progestin and adipoQ receptor family member VI, was genotyped in 216 patients and 216 control subjects and found to have significant differences in its genotype and allele frequencies (P = 0.0007, OR 2.02 and P = 0.0001, OR 2.02, respectively).
  
  
  CONCLUSIONS
  Our results suggest that these candidate genes are associated with KSD and PAQR6 comes into our view as the most potent candidate since associated SNP rs759330 is located in the miRNA binding site and may affect mRNA expression level.
authors.forename: Nanyawan
authors.initials: N
authors.lastname: Rungroj
authors.forename: Choochai
authors.initials: C
authors.lastname: Nettuwakul
authors.forename: Nirinya
authors.initials: N
authors.lastname: Sudtachat
authors.forename: Oranud
authors.initials: O
authors.lastname: Praditsap
authors.forename: Nunghathai
authors.initials: N
authors.lastname: Sawasdee
authors.forename: Suchai
authors.initials: S
authors.lastname: Sritippayawan
authors.forename: Duangporn
authors.initials: D
authors.lastname: Chuawattana
authors.affiliation: Division of Molecular Medicine, Department of Research and Development, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok 10700, Thailand. ptyench@gmail.com.
authors.forename: Pa-Thai
authors.initials: PT
authors.lastname: Yenchitsomanus
mesh_terms: D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D016022:Case-Control Studies; D019295:Computational Biology / Q000379:methods; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D055106:Genome-Wide Association Study; D005838:Genotype; D006239:Haplotypes; D006801:Humans; D007669:Kidney Calculi / Q000235:genetics*; D015810:Linkage Disequilibrium; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D055815:Young Adult