Effects of -1018G>A polymorphism of HRH2 (rs2607474) on the severity of gastric mucosal atrophy.
OBJECTIVE
Histamine plays important physiological roles in upper gastrointestinal tract and acts via the H2 receptor. A polymorphism -1018 G>A (rs2067474) was identified in an enhancer element of the HRH2 promoter. We attempted to clarify the associations of this polymorphism with the progression of gastric mucosal atrophy.


METHODS
Gastric mucosa samples were obtained from 398 subjects with no malignancies. The rs2067474 genotype was determined by PCR-SSCP method. The degree of gastritis was assessed in 366 subjects and serum pepsinogen (PG) I/II levels were measured in 108 subjects. The subjects with atrophy score higher or equal to 2 and metaplasia score higher or equal to1 were classified into the severe atrophic gastritis group (SA group).


RESULTS
The -1018G>A minor allele frequencies in SA and non-SA groups were 8.02% and 13.3%, respectively (p=0.057). The -1018 GG homozygote had a significantly high risk for gastric mucosal atrophy (OR: 2.03, 95%CI: 1.03-4.01, p=0.042). In H. pylori positive subjects, GG homozygote was a more significant risk factor for gastric mucosal atrophy (OR: 2.32, 95%CI: 1.12-4.81, p=0.023). In addition, in the subjects older than 60 years, GG homozygote had also a significant risk for gastric mucosal atrophy (OR: 2.63, 95%CI: 1.15-6.00, p=0.022). In -1018 GG homozygote, PG I/II ratio was significantly lower in H. pylori positive than negative subjects and was significantly decreased with age (p=0.0032 by ANOVA), whereas it was not in the A carrier.


CONCLUSIONS
Our results suggest that HRH2 -1018 GG homozygote is a risk factor for the severity of gastric mucosal atrophy under the influence of H. pylori infection, especially in older subjects.
Department of Gastroenterology, Kanazawa Medical University, 1-1 Daigaku, Uchinada-machi, Ishikawa, Japan.
Hideto
H
Yamada
Tomomitsu
T
Tahara
Hisakazu
H
Shiroeda
Ranji
R
Hayashi
Takashi
T
Saito
Masakatsu
M
Nakamura
Mutsumi
M
Tsuchishima
Mikihiro
M
Tsutsumi
Tomoyuki
T
Shibata
Tomiyasu
T
Arisawa
D000328:Adult; D000367:Age Factors; D000368:Aged; D005260:Female; D005753:Gastric Mucosa / Q000473:pathology; D005757:Gastritis, Atrophic / Q000201:enzymology / Q000235:genetics* / Q000382:microbiology; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D016481:Helicobacter Infections / Q000150:complications / Q000201:enzymology; D016480:Helicobacter pylori; D006579:Heterozygote; D006720:Homozygote; D006801:Humans; D008297:Male; D008875:Middle Aged; D020116:Pepsinogen A / Q000097:blood; D011110:Polymorphism, Genetic; D018807:Polymorphism, Single-Stranded Conformational; D011970:Receptors, Histamine H2 / Q000235:genetics*; D012720:Severity of Illness Index
D011970:Receptors, Histamine H2; D020116:Pepsinogen A