Association between intelectin-1 variation and human kidney stone disease in northeastern Thai population

An interplay of multiple genetic and environmental factors implicates an incidence of human kidney stone disease (KSD). However, the genetic factors associated with KSD are not completely known or understood. To identify KSD-associated genetic variations among the northeastern Thai patients, a genome-wide association study (GWAS) was conducted. We initially employed genotyping of single nucleotide polymorphism (SNP) using Genome-Wide Human SNP Array 6.0 in 105 patients and in 105 normal control subjects. To overcome the limitation of small sample size, we set forth to analyze SNPs as clusters based on the concept of linkage disequilibrium (LD) and haplotype. Using this analysis, 29 genes were identified. Three candidate SNPs, including rs2039415, rs2274907, and rs3747515, were selected on the basis of haplotype analysis, potentially functional SNPs, and the functions of associated genes. Further genotyping of these SNPs in a larger sample size (altogether 216 patients and 216 control subjects) showed that the candidate SNP rs2274907 remained significantly different between case and control subjects in both genotype frequencies (OR 2.44, 95% CI 1.38-4.30; p = 0.0015) and allele frequencies (OR 1.54, 95% CI 1.17-2.03; p = 0.0021). The non-synonymous SNP rs2274907 (c.326T > A) located in exon 4 of the ITLN1 gene results in a substitution of valine (V) by aspartate (D) at position 109 (p.V109D). This substitution could affect the predicted hydrogen (H)-bonds between lysine (K) 107 and glutamine (Q) 104, which supports its association with KSD in this population.