Genetic and phenotypic heterogeneity in tropical calcific pancreatitis

Abstract

Tropical calcific pancreatitis (TCP) is a form of chronic non-alcoholic pancreatitis initially reported in the developing parts of the tropical world. The clinical phenotype of TCP has undergone marked changes since its first description in 1968. The disease is now seen in relatively older people with less severe symptoms. In addition, there are varying reports on the proportion of cases presenting with imaging abnormalities like calcification, ductal dilation, and glandular atrophy. Significant progress has also been made in understanding the etiopathology of TCP. The role of malnutrition and cassava toxicity in its pathogenesis is disproven and few studies have focused on the role of micronutrient deficiency and oxidative stress in the etiopathogenesis of TCP. Emerging evidence support an important role for genetic risk factors in TCP. Several studies have shown that, rather than mutations in trypsinogens, variants in serine protease inhibitor kazal type 1, cathepsin B, chymotrypsin C, cystic fibrosis transmembrane regulator, and carboxypeptidase A1, predict risk of TCP. These studies also provided evidence of mutational heterogeneity between TCP and chronic pancreatitis in Western populations. The current review summarizes recent advances that have implications in the understanding of the pathophysiology and thus, heterogeneity in genotype-phenotype correlations in TCP.

Keywords: Chronic pancreatitis, Tropical calcific pancreatitis, Fibrocalculous pancreatic diabetes, Clinical phenotype, Genetic risk factors

Core tip: Tropical calcific pancreatitis (TCP) is a form of chronic pancreatitis of unknown etiology. The phenotype of TCP is quite heterogeneous and has undergone a marked change over the last few decades, such that only a small fraction of such cases represent classical TCP. Several studies have shown the important role of genetic factors in the pathophysiology of TCP and provide evidence of genetic and mutational heterogeneity, compared with that in Western countries. Hence, it is important to understand the genotype-phenotype correlation in TCP. This review summarizes recent developments that provide some understanding of genotypic and phenotypic heterogeneity in this enigmatic disease.