幽门螺杆菌诱导的高危萎缩性胃炎和胃癌中微小RNA的基因多态性
Gene polymorphisms of micrornas in Helicobacter pylori-induced high risk atrophic gastritis and gastric cancer.
作者信息
Kupcinskas Juozas, Wex Thomas, Link Alexander, Leja Marcis, Bruzaite Indre, Steponaitiene Ruta, Juzenas Simonas, Gyvyte Ugne, Ivanauskas Audrius, Ancans Guntis, Petrenkiene Vitalija, Skieceviciene Jurgita, Kupcinskas Limas, Malfertheiner Peter
机构信息
Institute for Digestive Research, Lithuanian University of Health Sciences, Kaunas, Lithuania ; Department of Gastroenterology, Lithuanian University of Health Sciences, Kaunas, Lithuania.
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.
出版信息
PLoS One. 2014 Jan 27;9(1):e87467. doi: 10.1371/journal.pone.0087467. eCollection 2014.
BACKGROUND AND AIMS
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.
背景与目的
微小RNA（miRNA）作为肿瘤抑制基因或癌基因的翻译调节因子而为人所知。miRNA相关基因中的单核苷酸多态性（SNP）已被证明会影响miRNA的调节能力，并与胃癌（GC）及癌前胃部病变有关。本研究的目的是评估miRNA相关基因多态性（miR-27a、miR-146a、miR-196a-2、miR-492和miR-608）与欧洲人群中GC或高危萎缩性胃炎（HRAG）的存在之间的潜在关联。
方法
对995名欧洲血统受试者（对照组：n = 351；GC组：n = 363；HRAG组：n = 281）的基因多态性进行分析。通过逆转录聚合酶链反应（RT-PCR）对miR-27a T>C（rs895819）、miR-146a G>C（rs2910164）、miR-196a-2 C>T（rs11614913）、miR-492 G>C（rs2289030）和miR-608 C>G（rs4919510）的SNP进行基因分型。
结果
总体而言，miRNA的SNP与GC或HRAG的存在无关。我们观察到，与CC基因型相比，miR-196a-2 CT基因型有与GC更高风险相关的趋势，然而，差异未达到校正P值（优势比（OR）- 1.46，95%置信区间（CI）1.03 - 2.07，P = 0.032）。与对照组相比，miR-608 GG基因型在GC中更常见（OR -2.34，95% CI 1.08 - 5.04），但显著性仍很微弱（P = 0.029）。在miR-608的隐性模型中观察到类似趋势，其中CC + CG与GG基因型比较显示GC风险增加的趋势，OR为2.44（95% CI 1.14 - 5.22，P = 0.021）。miR-27a、miR-146a、miR-196a-2、miR-492和miR-608 SNP的基因型和等位基因在GC的组织学亚型之间具有相似的分布，并且与弥漫型或肠型GC的存在无关。
结论
在欧洲受试者中，miR-27a、miR-146a、miR-196a-2、miR-492、miR-492a和miR-608的基因多态性与HRAG、GC或GC的不同组织学亚型的存在无关。
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