Frequency of CFTR, SPINK1, and Cathepsin B Gene Mutation in North Indian Population: Connections between Genetics and Clinical Data

Shweta Singh,Gourdas Choudhuri,Sarita Agarwal

doi:10.1155/2014/763195

Abstract

Objectives. Genetic mutations and polymorphisms have been correlated with chronic pancreatitis (CP). This study aims to investigate the association of genetic variants of cystic fibrosis transmembrane conductance regulator (CFTR) and serine protease inhibitor Kazal type 1 (SPINK-1) genes and Cathepsin B gene polymorphisms with CP and to associate genetic backgrounds with clinical phenotypes. Methods. 150 CP patients and 150 normal controls were enrolled consecutively. We analyzed SPINK-1 N34S and IVS3+2T>C gene mutations by PCR-restriction-fragment length polymorphism (RFLP). The identification of DF508, G551D, G542X, R117H, and W1282X mutations was carried out by ARMS-PCR. S549N mutation, IVS8 polyTn polymorphism, and Cathepsin B Lec26Val were analysed by PCR-RFLP, nested PCR, and PCR-RFLP plus sequencing, respectively. Results. We found a significant association of SPINK1 (N34S) gene polymorphism. IVS1−37T>C polymorphism shows linkage with 101A>G. 300 chromosomes belonging to the CFTR subgroup exhibited minor allele frequency of 0.04, 0.03, 0.03, 0.013, 0.006, and 0.02 for DF508, G452X, G551D, S549N, R117H, and IVS8 T5, respectively. Except for R117H and IVS8 T5 polymorphisms, all other mutations showed significant variation. Conclusion. Analysis of potential susceptibility variants is needed to support nature of the genes and environment in pancreatitis. This data may help establish genetic screening and prenatal setup for Indian population.

Highlights

Pancreatitis is inflammatory diseases characterized by multifactorial pathogeneses
IVS1−37T>C polymorphism shows linkage with 101A>G. 300 chromosomes belonging to the CFTR subgroup exhibited minor allele frequency of 0.04, 0.03, 0.03, 0.013, 0.006, and 0.02 for DF508, G452X, G551D, S549N, R117H, and IVS8 T5, respectively
Mutation in the cystic fibrosis gene is associated with idiopathic chronic pancreatitis when present in heterozygous state in association with other CFTR polymorphism [7]

Summary

Introduction

Pancreatitis is inflammatory diseases characterized by multifactorial pathogeneses. Chronic pancreatitis is characterized by parenchymal changes including inflammation, fibrosis, and loss of exocrine and endocrine tissue. Chronic Pancreatitis (CP) occurs in association with exogenous and endogenous factors including alcohol intake, smoking habits, pancreas divisum, sphincter of Oddi dysfunction, and/or a genetic predisposition [1,2,3,4,5]. The familial clustering of TCP suggests that genetic defect may predispose to the disease. The environmental factors may be operative on the background of a genetic predisposition to pancreatitis [6]. Mutation in the cystic fibrosis gene is associated with idiopathic chronic pancreatitis when present in heterozygous state in association with other CFTR polymorphism [7]. Combined data from other studies indicated that ∼18%

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Conclusion