Sequence analysis of the genes encoding for H+/K+-ATPase in autoimmune gastritis.
BACKGROUND
H+/K+-ATPase is the target autoantigen in autoimmune gastritis (AIG), an organ-specific autoimmune disease with a strong hereditary component.


OBJECTIVE
To detect possible polymorphisms in H+/K+-ATPase alpha- and beta-subunits in AIG patients.


METHODS
Blood samples from 12 Finnish AIG patients were sequenced for the coding regions of genes encoding for H+/K+-ATPase alpha- and beta-subunits; 50-52 Finnish anonymous blood donors served as controls. Additionally, parietal cell and Helicobacter pylori antibodies and serum pepsinogen I levels (PG I) were analysed.


RESULTS
In the alpha-subunit, all patients and controls had C-allele at the non-synonymous c.824T>C single nucleotide polymorphism (SNP) resulting in valine substitution for alanine (Val265Ala). In the beta-subunit, a previously unknown non-synonymous SNP resulting in a substitution of alanine residue for valine (Ala248Val) was found in exon 7 in a single patient and none of the controls. All patients had low serum PG I levels and elevated parietal cell antibodies; three had positive H. pylori serology.


CONCLUSIONS
At the non-synonymous SNP c.824T>C in the alpha-subunit of H+/K+-ATPase most Finnish individuals with or without AIG have C allele. Genetic variants of the coding regions of genes for H+/K+-ATPase alpha- and beta-subunits are not associated with AIG in Finnish patients.
Oksanen
Aino M
AM
Herttoniemi Municipal Hospital, and Department of Medical Genetics, University of Helsinki, Finland. aino.oksanen@hel.fi
Lemmelä
Susanna M
SM
Järvelä
Irma E
IE
Rautelin
Hilpi I
HI
D000328:Adult; D000907:Antibodies, Bacterial / Q000097:blood*; D001323:Autoantibodies / Q000097:blood; D001327:Autoimmune Diseases / Q000097:blood / Q000235:genetics* / Q000276:immunology; D005260:Female; D005387:Finland; D005757:Gastritis, Atrophic / Q000097:blood / Q000235:genetics* / Q000276:immunology; D005787:Gene Frequency; D016480:Helicobacter pylori / Q000276:immunology*; D006801:Humans; D008297:Male; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood; D020641:Polymorphism, Single Nucleotide; D021122:Protein Subunits / Q000235:genetics; D017422:Sequence Analysis, DNA; D000254:Sodium-Potassium-Exchanging ATPase / Q000235:genetics* / Q000276:immunology
D000907:Antibodies, Bacterial; D001323:Autoantibodies; D021122:Protein Subunits; D020116:Pepsinogen A; D000254:Sodium-Potassium-Exchanging ATPase