Genetic Polymorphisms of RGS14 and Renal Stone Disease

Background: Renal stone disease (RSD) is a common disease of the human urinary system and is regarded as a multifactorial condition affected by environmental and genetic factors. RGS14 encodes a complex scaffolding protein, known as regulator of G protein signaling 14, which is enriched in hippocampal area CA2 dendritic spines.

Aim of the study: We aimed to investigate the association between genetic polymorphisms in RGS14 and the risk of RSD based on a large sample of the Chinese Han population.

Methods: A total of 1,436 subjects, comprising 506 patients with RSD and 920 controls, were enrolled in the study. Ten tag SNPs located in the RGS14 gene region were chosen for genotyping. Genetic associations were evaluated at both the single marker and haplotype levels. Genotypic (χ² test) and allelic analyses (Cochran-Armitage test for trend) were performed for single marker-based association. Two bioinformatics tools, RegulomeDB and GTEx, were used to examine the functional consequences of the target SNP.

Results: SNP rs11746443 was found to be significantly associated with disease status (χ² = 12.60, p = 0.0018). Moreover, the A allele of this SNP was significantly associated with an increased risk of RSD (OR [95%CI] = 1.36 [1.13-1.65]). Multiple significant eQTL signals of rs11746443 on RGS14 were identified.

Conclusions: This study replicated the association signal of RGS14 with RSD in a large sample of the Chinese Han population. The results suggest that the SNP rs11746443 of RGS14 might increase the risk of RSD by regulating the Ca²⁺ levels in humans.