Abstract
[Background] A polymorphism rs7521584 is located between MIR200B and MIR 429. Recently, it has been reported that both miR200 and miR429 target c-myb gene and affect the breast cancer cell growth (Cesi V, et al.: Cell cycle 2011). One of both the miR200s and miR429 targeting genes is RIPK2, coding RICK. RICK is an important molecule for inflammation by transmitting NOD signal. Then, we attempted to clarify the association between chronic gastritis and genomic variation rs7521584G>T in Japanese population. [Materials and Methods] Gastric mucosa samples were obtained from 429 subjects with no malignancies. The rs7521584 genotype was determined by PCR-SSCP method using DNA extracted from obtained gastric mucosa. The degree of gastritis was assessed in 393 cases according to the updated Sydney system, serum pepsinogen (PG) I/II levels were measured in 117 cases. [Results] The mean age of the subjects was 59.7 years old, male/female ratio was 253/176, and H. pylori (HP) positive ratio was 63.6%. The distribution of rs7521584G>T genotype in all subjects was 153GG, 215GT and 61TT (HWE, p=0.31). The atrophic gastritis group (GA group) was defined as atrophy score >0 and metaplasia score >0. Then, the distribution of rs7521584G>T genotype in GA group (n=142) was 51GG, 66GT and 22TT. The rs7521584 minor allele frequencies in GA and non-GA groups were 39.6% and 38.2%, respectively. By logistic regression analysis after adjustment for gender, age and H. pylori (HP) infection status, rs7521584 TT homozygote has a significantly high risk for gastric mucosal atrophy (OR: 2.41, 95%CI: 1.10-5.25, p=0.027). In HP positive subjects, TT homozygote was a more significant risk factor for gastric mucosal atrophy (OR: 3.31, 95%CI: 1.35-8.12, p=0.0089). In addition, in the subjects younger than 60 years old, TT homozygote has also significant risk for gastric mucosal atrophy (OR: 3.15, 95%CI: 1.03-9.61, p=0.044). The serum PG I/II ratio was reversely correlated to the age in TT homozygote (p=0.0084 by ANOVA), whereas there was no correlation between age and PG I/II ratio in G carrier (p=0.092). [Conclusions] Our results suggest that rs7521584, in pre-miR429 and premiR200s gene, TT homozygote is a risk factor for the progression of gastric mucosal atrophy under the influence of HP infection.
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