Microsatellite Scan Identifies New Candidate Genes for Susceptibility to Alcoholic Chronic Pancreatitis in Japanese Patients

Abstract

Alcohol abuse is one of the most common risk factor for chronic pancreatitis, but the underlying pathophysiological mechanisms remain unclear. The aim of this study was to identify genes that contribute to susceptibility or resistance for alcoholic chronic pancreatitis by screening the whole genome. Sixty-five patients with alcoholic chronic pancreatitis (63 men and 2 women, mean age 55.2 years) and 99 healthy Japanese controls were enrolled in this study. This was an association study using 400 polymorphic microsatellite markers with an average spacing of 10.8 cM distributed throughout the whole genome. This search revealed 10 candidate susceptibility regions and 5 candidate resistant regions throughout the genome. No specific microsatellite markers were detected in association with previously reported susceptibility genes for chronic pancreatitis, such as PRSS1, PRSS2, CTRC, SPINK1, CFTR, ALDH2, and CYP2E1. Among the statistically significant markers, D15S1007 on chromosome 15q14 showed strong evidence for disease susceptibility (70.8% vs. 35.1%, Pc = 0.0001). Within 500 kb of D15S1007, several genes were candidate genes for susceptibility, including FMN1, DKFZP686C2281, LOC440268, RYR3, and AVEN, This study identified 10 candidate susceptibility and 5 candidate resistant regions that may contain genes involved in ACP pathogenesis.

The Common Chymotrypsinogen C ( CTRC ) Variant G60G (C.180T) Increases Risk of Chronic Pancreatitis But Not Recurrent Acute Pancreatitis in a North American Population

“… 1 PCR primers were designed for CTRC gene exons 2, 3, and 7 and the corresponding intronic regions that contain most of the commonly reported mutations reported in Germany, India, France, and Taiwan. 40 , 41 , 47 , 48 , 53 …”

Genetics of pancreatitis

“…This underscores the difficulty of collecting a ‘healthy alcoholic’ control group as well as the limited understanding of the complex genetic factors. Other small studies have had negative results for the standard genetic risk factors [44], but there have been some advances in identifying novel genetic risk factors in alcohol-induced pancreatitis [45]. Common polymorphisms in alcohol metabolism genes, such as ALDH1, ALDH3, and ADH, have been implicated as either protective or damaging factors for alcoholic pancreatitis in Europe and Asia [46,47], whereas North American similar studies are ongoing.…”

Genome-Wide Screening for Risk Loci of Idiopathic Recurrent Miscarriage in a Han Chinese Population: A Pilot Study

“…Genome-wide study using microsatellite markers has been successfully performed to identify genetic risk factors of complex disorders. 19,20 Microsatellites (also called short tandem repeat polymorphisms) are tandem arrays of short stretches of nucleotide sequences that are usually repeated between 15 and 30 times. 21,22 The advantages of microsatellites are high heterozygosity, ubiquity throughout the genome, relative stability, and conservation for every individual and easy genotyping by polymerase chain reaction (PCR).…”