Genetic aspects of tropical calcific pancreatitis

Abstract

Tropical calcific pancreatitis (TCP) is a subtype of chronic pancreatitis which is unique to tropical regions. Patients present at young age with recurrent abdominal pain, nutritional deficiencies, and insulin-requiring diabetes. For a long time, the aetiology of this disorder was poorly understood. Several environmental factors, such as malnutrition or the consumption of toxic food components such as cyanogenic glycosides, were proposed as pathogenic factors. In the last decade, a major impact on the understanding of the aetiology of TCP has come from genetic studies on hereditary and idiopathic chronic pancreatitis. Genetic alterations in at least five genetic loci are clearly associated with chronic pancreatitis in the Western world. These include alterations in genes coding for trypsinogens, the most abundant digestive enzymes (PRSS1 and PRSS2), the trypsin inhibitor (SPINK1) and the trypsin-degrading enzyme, chymotrypsinogen C (CTRC). In addition, alterations in the cystic fibrosis (CFTR) gene are associated with idiopathic pancreatitis. TCP clinically resembles non-alcoholic chronic pancreatitis of Western countries, suggesting that similar genetic defects might also be of importance in this disease entity. Indeed, alterations in at least two genes, SPINK1 and CTRC, are strongly associated with TCP. The current review focuses on the recent developments in the understanding of the genetic basis of inherited pancreatitis, with special emphasis on TCP.

Polyethylenimine-grafted polycarbonates as biodegradable polycations for gene delivery

“…Gene therapy has been attracting more attentions for the treatment of genetic and acquired diseases that are currently incurable, such as immunodeficiency [1], cystic fibrosis [2], and Parkinson's disease [3]. In response, two primary gene vehicle classes have been developed: recombinant viruses and non-viral vectors [4].…”

A Case of Chronic Calcific Nonalcoholic Pancreatitis

“…It occurs most often in the second and third decades of life [1]. It is associated with the development of insulin-dependent diabetes mellitus in approximately 90% of patients, often before the age of 30 [2, 3]. When diabetes is present, the condition may also be referred to as FCPD [1].…”

“…However, TCP has been reported in populations where cassava is not consumed [5], and prolonged cassava consumption did not produce pancreatitis in the rat model [7]. It has also been reported in patients with no history of cassava in their diets, from higher socioeconomic groups, and in familial clusters suggesting other contributing factors [2]. …”

The G191R variant in the PRSS2 gene does not play a role in protection against tropical calcific pancreatitis

“…Thus, it may be surmised that the protective PRSS2 variant has only marginally penetrated the Indians possibly because it does not play an important role in protection against TCP. Although a recent study speculated a protective role to G191R polymorphism in TCP based on analysis of 174 patients and 794 control subjects from north and south India, the study did not reach statistical significance (p = 0.48) 6. Considering the small sample size of north Indian control subjects (n = 84), any assumptions on role of differing allele frequency for G191R variant in various parts of India remains a matter of debate 6…”