Analysis of the Alcohol Dehyrogenase (ADH3) and the Serine Protease Inhibitor, Kazal type 1 (SPINKl) Genes in Alcohol-Induced Pancreatitis
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Authors
Kilar, Margaret A.
Issue Date
2004
Type
Thesis
Language
en_US
Keywords
Alternative Title
Abstract
Alcohol dehydrogenase (ADH3) polymorphisms and serine protease inhibitor,
Kazal type 1 (SPINK1) mutations, particularly N34S, have been examined in
pancreatitis patients, although no study has analyzed both genes in the same patient.
Previous studies suggested a possible association between ADH3 or SPINKI and
alcohol induced pancreatitis; however, a statistically significant association was not
proven. We hypothesize that ADH3 polymorphisms and SPINK 1 mutations are
associated with alcohol-induced pancreatitis. Three groups were analyzed in this
study: Patients with alcohol-induced pancreatitis (N = 45), non-alcohol associated
pancreatitis with a positive family history of pancreatitis (N = 8) and non-alcohol
associated pancreatitis with a negative family history of pancreatitis (N = 51). The
ADH3 * 1 and *2 polymorphisms were analyzed by restriction fragment length
polymorphism (RFLP) analysis. SPINKI exon 3 was analyzed by direct DNA
sequencing to identify previously known mutations including N34S, P55S and
IVS3+2T →C. The ADH3 * 1 and *2 allele frequency among Caucasian alcohol
associated and non-alcohol associated pancreatitis patients was 0.5 and 0.5,
respectively. The ADH3 *1 and *2 allele frequency among African American
alcohol associated and non-alcohol associated pancreatitis patients was 0.8 and 0.2,
respectively. The ADH3*2 allele, associated with a lower rate of alcohol
metabolism, was detected at a higher frequency among African American pancreatitis
patients (regardless of alcohol intake status), compared to the expected allele
frequency, based on normal controls. SPINKI mutations were only identified among
patients with non-familial, non-alcohol induced pancreatitis. Six of fifty-one patients
(11.8%) had at least one SPINKl mutation, including N34S, P55S, IVS3+2T →C, and
a novel V 46D mutation. One individual was compound heterozygous for N34S and
IVS3+ 2T →C. Our SPINK1 results are in agreement with previous findings, that
SPINK1 mutations are associated with non-familial idiopathic pancreatitis but are not
likely involved in alcohol-induced pancreatitis among Caucasians or African
Americans. Our ADH3 results differ from previous studies of alcohol-induced
pancreatitis, suggesting an association of this disease with the ADH3 *2 allele in
African Americans. This study, and similar studies, may be clinically relevant for
future pancreatitis genetic testing.
Description
viii, 29 p.
Citation
Publisher
Kalamazoo College
License
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