Homozygous (TG)11 allele in intron 8 of the cystic fibrosis transmembrane conductance regulator (CFTR) gene has a protective role against bicarbonate decrease in pure pancreatic juice among Japanese male alcoholics.
BACKGROUND
Heavy drinkers have a high incidence of chronic pancreatitis (CP), but the mechanism of alcohol-related CP is largely unknown. Exocrine pancreatic insufficiency exists in about 90% of the patients with cystic fibrosis (CF), which results from an abnormal cystic fibrosis transmembrane conductance regulator gene (CFTR).


OBJECTIVE
To investigate in Japanese alcoholics the association between bicarbonate concentration in pure pancreatic juice and one of the polymorphisms of the CFTR gene, the (TG)m Tn tract length in intron 8.


METHODS
Fifty-six patients under treatment for alcohol dependence were stimulated by intravenous injection of secretin during endoscopic retrograde cholangiopancreatography to provide pancreatic juice specimens. Individual maximum bicarbonate concentrations (MBC) were compared with (TG)m Tn tract polymorphisms identified by directly sequencing lymphocyte DNA.


RESULTS
Among the 41 patients able to provide adequate pancreatic juice specimens, 15 had low MBC and 26 had normal MBC. The frequencies of the six haplotypes identified in these patients were 17.1% (TG)11T7/(TG)llT7, 46.3% (TG)11T7/(TG)12T7, 29.3% (TG)12T7/(TG)12T7, 2.4% (TG)10T9/(TG)11T7, 2.4% (TG)12T5/(TG)11T7, and 2.4% (TG)12T6/(TG)12T7. Among the 92.7% of patients who had the common (TG) miT7/(TG)m2T7 haplotype, all of the 7 with homozygous (TG)11 alleles had normal MBC (p<0.05).


CONCLUSIONS
Alcoholics with homozygous (TG)11 alleles in intron 8 of the CFTR gene appear to be protected against decreased MBC, compared with those who have the (TG)11/(TG)12 and (TG)12/(TG)12 genotypes, suggesting a role for CFTR gene polymorphism in the progression of alcohol-related pancreatic disease.
Nakamura
Yuji
Y
National Hospital Organization, Kurihama Alcoholism Center, Nobi, Yokosuka, Kanagawa 239-0841.
Ohmori
Tomohiro
T
Ishikawa
Akiko
A
Kobayashi
Yasunori
Y
Imazeki
Hiromi
H
Higuchi
Susumu
S
Maruyama
Katsuya
K
D000328:Adult; D000483:Alleles; D001639:Bicarbonates / Q000032:analysis*; D002908:Chronic Disease; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics*; D020022:Genetic Predisposition to Disease; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D010189:Pancreatic Juice / Q000737:chemistry*; D019512:Pancreatitis, Alcoholic / Q000235:genetics* / Q000378:metabolism; D011110:Polymorphism, Genetic; D017422:Sequence Analysis, DNA
D001639:Bicarbonates; C505032:CFTR protein, human; D019005:Cystic Fibrosis Transmembrane Conductance Regulator