RGD Reference Report - Functional characteristics of L1156F-CFTR associated with alcoholic chronic pancreatitis in Japanese. - Rat Genome Database

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Functional characteristics of L1156F-CFTR associated with alcoholic chronic pancreatitis in Japanese.

Authors: Kondo, S  Fujiki, K  Ko, SB  Yamamoto, A  Nakakuki, M  Ito, Y  Shcheynikov, N  Kitagawa, M  Naruse, S  Ishiguro, H 
Citation: Kondo S, etal., Am J Physiol Gastrointest Liver Physiol. 2015 Aug 15;309(4):G260-9. doi: 10.1152/ajpgi.00015.2014. Epub 2015 Jun 18.
RGD ID: 11566036
Pubmed: PMID:26089335   (View Abstract at PubMed)
PMCID: PMC4537928   (View Article at PubMed Central)
DOI: DOI:10.1152/ajpgi.00015.2014   (Journal Full-text)

Although cystic fibrosis is rare in Japanese, measurement of sweat Cl(-) has suggested mild dysfunction of cystic fibrosis transmembrane conductance regulator (CFTR) in some patients with chronic pancreatitis. In the present study, we have investigated the association of CFTR variants and chronic pancreatitis in Japanese and the functional characteristics of a Japanese- and pancreatitis-specific CFTR variant, L1156F. Seventy patients with alcoholic chronic pancreatitis, 18 patients with idiopathic chronic pancreatitis, and 180 normal subjects participated. All exons and their boundaries and promoter region of the CFTR gene were sequenced. Human embryonic kidney-293 cells were transfected with three CFTR variants (M470V, L1156F, and M470V+L1156F), and the protein expression was examined. Xenopus laevis oocytes were injected with the CFTR variants, and bicarbonate (HCO3 (-)) transport activity was examined. CFPAC-1 cells were transfected with the CFTR variants and Cl(-)/HCO3 (-) exchange activity was examined. Six variants (E217G, I556V, M470V, L1156F, Q1352H, and R1453W) were identified in the coding region of the CFTR gene. Cystic fibrosis-causing mutations were not found. The allele frequencies of L1156F and Q1352H in alcoholic chronic pancreatitis (5.0 and 7.9%) were significantly (P < 0.01) higher than those in normal subjects (0.6 and 1.9%). L1156F was linked with a worldwide CFTR variant, M470V. Combination of M470V and L1156F significantly reduced CFTR expression to approximately 60%, impaired CFTR-mediated HCO3 (-)/Cl(-) transport activity to 50-60%, and impaired CFTR-coupled Cl(-)/HCO3 (-) exchange activity to 20-30%. The data suggest that the Japanese-specific CFTR variant L1156F causes mild dysfunction of CFTR and increases the risk of alcoholic chronic pancreatitis in Japanese.

RGD Manual Disease Annotations    Click to see Annotation Detail View
TermQualifierEvidenceWithReferenceNotesSourceOriginal Reference(s)
alcoholic pancreatitis  IAGP 11566036DNA:missense mutations: :p.L1156F and Q1352H (human)RGD 
alcoholic pancreatitis  ISOCFTR (Homo sapiens)11566036; 11566036DNA:missense mutations: :p.L1156F and Q1352H (human)RGD 

Objects Annotated

Genes (Rattus norvegicus)
Cftr  (CF transmembrane conductance regulator)

Genes (Mus musculus)
Cftr  (cystic fibrosis transmembrane conductance regulator)

Genes (Homo sapiens)
CFTR  (CF transmembrane conductance regulator)


Additional Information