Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer.
OBJECTIVE
MicroRNAs (miRNAs) are known for their function as translational regulators of tumor suppressor or oncogenes. Single nucleotide polymorphisms (SNPs) in miRNAs related genes have been shown to affect the regulatory capacity of miRNAs and were linked with gastric cancer (GC) and premalignant gastric conditions. The purpose of this study was to evaluate potential associations between miRNA-related gene polymorphisms (miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608) and the presence of GC or high risk atrophic gastritis (HRAG) in European population.


METHODS
Gene polymorphisms were analyzed in 995 subjects (controls: n = 351; GC: n = 363; HRAG: n = 281) of European descent. MiR-27a T>C (rs895819), miR-146a G>C (rs2910164), miR-196a-2 C>T (rs11614913), miR-492 G>C (rs2289030) and miR-608 C>G (rs4919510) SNPs were genotyped by RT-PCR.


RESULTS
Overall, SNPs of miRNAs were not associated with the presence of GC or HRAG. We observed a tendency for miR-196a-2 CT genotype to be associated with higher risk of GC when compared to CC genotype, however, the difference did not reach the adjusted P-value (odds ratio (OR) - 1.46, 95% confidence interval (CI) 1.03-2.07, P = 0.032). MiR-608 GG genotype was more frequent in GC when compared to controls (OR -2.34, 95% CI 1.08-5.04), but significance remained marginal (P = 0.029). A similar tendency was observed in a recessive model for miR-608, where CC + CG vs GG genotype comparison showed a tendency for increased risk of GC with OR of 2.44 (95% CI 1.14-5.22, P = 0.021). The genotypes and alleles of miR-27a, miR-146a, miR-196a-2, miR-492 and miR-608 SNPs had similar distribution between histological subtypes of GC and were not linked with the presence of diffuse or intestinal-type GC.


CONCLUSIONS
Gene polymorphisms of miR-27a, miR-146a, miR-196a-2, miR-492, miR-492a and miR-608 were not associated with the presence of HRAG, GC or different histological subtypes of GC in European subjects.
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania ; Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Juozas
J
Kupcinskas
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany ; Medical Laboratory for Clinical Chemistry, Microbiology and Infectious Diseases, Department of Molecular Genetics, Magdeburg, Germany.
Thomas
T
Wex
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany.
Alexander
A
Link
Faculty of Medicine, University of Latvia, Riga, Latvia ; Digestive Diseases Center GASTRO, Riga, Latvia ; Riga East University Hospital, Riga, Latvia.
Marcis
M
Leja
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Indre
I
Bruzaite
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Ruta
R
Steponaitiene
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Simonas
S
Juzenas
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Ugne
U
Gyvyte
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Audrius
A
Ivanauskas
Digestive Diseases Center GASTRO, Riga, Latvia ; Riga East University Hospital, Riga, Latvia.
Guntis
G
Ancans
Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Vitalija
V
Petrenkiene
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Jurgita
J
Skieceviciene
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania ; Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
Limas
L
Kupcinskas
Department of Gastroenterology, Hepatology and Infectious Diseases, Otto von Guericke University, Magdeburg, Germany.
Peter
P
Malfertheiner
D005757:Gastritis, Atrophic / Q000235:genetics* / Q000382:microbiology*; D016480:Helicobacter pylori; D006801:Humans; D016015:Logistic Models; D035683:MicroRNAs / Q000235:genetics*; D016017:Odds Ratio; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D013274:Stomach Neoplasms / Q000235:genetics*; D044465:White People / Q000235:genetics
D035683:MicroRNAs