Common calcium-sensing receptor (CASR) gene variants do not modify risk for chronic pancreatitis in a Hungarian cohort

Abstract

The calcium-sensing receptor (CASR) is expressed in the pancreas where it might regulate calcium concentrations in pancreatic secretions. Two independent studies reported conflicting results claiming that commonly occurring missense variants of the CASR gene are risk factors for chronic pancreatitis (CP). Here, we attempted to replicate the association between CASR variants and CP. We analyzed 337 patients and 840 controls from the Hungarian National Pancreas Registry either by direct sequencing of exon 7 and the flanking noncoding regions or by TaqMan SNP genotyping assays. We identified two common missense variants, c.2956G>T (p.A986S), and c.2968A>G (p.R990G), three low-frequency variants, c.3031C>G (p.Q1011E), c.2610G>A (p.E870=) and c.∗60T>A, and 8 rare variants including the novel variant c.1895G>A (p.G632D). When allelic or genotype distributions were considered, none of the CASR variants associated with CP. Subgroup analysis of nonalcoholic versus alcoholic patients revealed no disease association either. Our results demonstrate that common CASR variants do not modify the risk for CP and should not be considered as genetic risk factors in the clinical setting.

Keywords: Calcium-sensing receptor; Genetic association study; Pancreatitis; Variants.

Figure 1.

Snakeplot showing the calcium-sensing receptor (CASR) missense variants found in the Hungarian cohort. The amino acids coded by exon 7 are highlighted with light grey, rare missense variants p.N592S, p.G632D, and p.N802S are shown in dark gray, while common variants p.A986S, and p.R990G, and low-frequency variant p.Q1011E are depicted in black. The snakeplot was generated by GPCRdb [34].