Dataset Information

Interactions of miR-34b/c and TP53 polymorphisms on the risk of intracranial aneurysm.

ABSTRACT: Several lines of evidence indicate that inflammatory processes play a key role in the happening and development of intracranial aneurysm (IA). Recently, polymorphisms in the TP53 gene were shown to be associated with inflammation and inflammatory disease. The aim of this study was to investigate the interactions of miR-34b/c and TP53 Arg72-Pro polymorphisms on the risk of IA in a Chinese population. A total of 590 individuals (including 164 patients with IA and 426 controls) were involved in this study. The polymorphisms (i.e., miR-34b/c rs4938723 and TP53 Arg72-Pro) were genotyped by polymerase chain reaction-restriction fragment length polymorphism assay and DNA sequencing. We found that the CC genotype of miR-34b/c rs4938723 was significantly associated with a decreased risk of IA compared with the TT genotype. Moreover, a significant gene interaction of the carriers with the combined genotypes of miR-34b/c rs4938723CC and TP53 Arg72Pro CG/CC/GG had a decreased risk of IA, compared with those carrying miR-34b/c rs4938723CT/TT+TP53 Arg72Pro GG/CG/CC combined genotypes. These findings suggest that the miR-34b/c rs4938723CC and TP53 Arg72-Pro polymorphisms may be involved in the susceptibility to IA.

SUBMITTER: Li L

PROVIDER: S-EPMC3403301 | biostudies-literature | 2012

REPOSITORIES: biostudies-literature

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Interactions of miR-34b/c and TP53 polymorphisms on the risk of intracranial aneurysm.

Li Lijuan L Sima Xiutian X Bai Peng P Zhang Lushun L Sun Hong H Liang Weibo W Liu Jianxing J Zhang Lin L Gao Linbo L

Clinical & developmental immunology 20120711

Several lines of evidence indicate that inflammatory processes play a key role in the happening and development of intracranial aneurysm (IA). Recently, polymorphisms in the TP53 gene were shown to be associated with inflammation and inflammatory disease. The aim of this study was to investigate the interactions of miR-34b/c and TP53 Arg72-Pro polymorphisms on the risk of IA in a Chinese population. A total of 590 individuals (including 164 patients with IA and 426 controls) were involved in thi ...[more]

PMID: 22844323

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Project description:BackgroundGenetic polymorphisms of pri-miR-34b/c and pre-miR-196a2 have been reported to be associated with the susceptibility to cancers. However, the effect of these polymorphisms and their interactions with hepatitis B virus (HBV) mutations on the development of hepatocellular carcinoma (HCC) remains largely unknown. We hypothesized that these polymorphisms might interact with the HBV mutations and play a role in hepatocarcinogenesis.MethodsPri-miR-34b/c rs4938723 (T>C) and pre-miR-196a2 rs11614913 (T>C) were genotyped in 3,325 subjects including 1,021 HBV-HCC patients using quantitative PCR. HBV mutations were determined by direct sequencing. Contributions of the polymorphisms and their multiplicative interactions with gender or HCC-related HBV mutations to HCC risk were assessed using multivariate regression analyses.Resultsrs4938723 CC genotype was significantly associated with HCC risk compared to HBV natural clearance subjects, adjusted for age and gender (adjusted odds ratio [AOR]?=?2.01, 95% confidence interval [CI]?=?1.16-3.49). rs4938723 variant genotypes in dominant model significantly increased HCC risk in women, compared to female healthy controls (AOR?=?1.85, 95% CI?=?1.20-2.84) or female HCC-free subjects (AOR?=?1.62, 95% CI?=?1.14-2.31). rs4938723 CC genotype and rs11614913 TC genotype were significantly associated with increased frequencies of the HCC-related HBV mutations T1674C/G and G1896A, respectively. rs11614913 was not significantly associated with HCC risk, but its CC genotype significantly enhanced the effect of rs4938723 in women. In multivariate regression analyses, rs4938723 in dominant model increased HCC risk (AOR?=?1.62, 95% CI?=?1.05-2.49), whereas its multiplicative interaction with C1730G, a HBV mutation inversely associated with HCC risk, reduced HCC risk (AOR?=?0.34, 95% CI?=?0.15-0.81); rs11614913 strengthened the G1896A effect but attenuated the A3120G/T effect on HCC risk.Conclusionsrs4938723 might be a genetic risk factor of HCC but its effect on HCC is significantly affected by the HBV mutations. rs11614913 might not be a HCC susceptible factor but it might affect the effects of the HBV mutations or rs4938723 on HCC risk.

Project description:BackgroundAneuploidy pregnancy is a severe major birth defect and causes about 50% spontaneous miscarriages with unknown etiology. To date, only a few epidemiological studies with small sample sizes have investigated the risk factors for aneuploidy pregnancy. TP53, MDM2, and miR-34b/c genes are implicated in tumorigenesis with aneuploidy, yet the function of their polymorphisms in aneuploidy pregnancy susceptibility needs to be clarified.ObjectiveTo elucidate the association of TP53 rs1042522 G > C, MDM2 rs2279744 309 T > G, and miR-34b/c rs4938723 T > C specific polymorphisms with aneuploidy pregnancy.MethodsIn the retrospective case-control study, 330 aneuploidies pregnancy women and 813 normal pregnancy controls were recruited between January 2018 and April 2022 at the First People's Hospital of Yunnan Province, Kunming, China. Three functional polymorphisms, the TP53 rs1042522 G > C (Arg72Pro), MDM2 rs2279744 309 T > G, and miR-34b/c rs4938723 T > C, were genotyped using the snapshot method.ResultsThe frequency distribution of three genotypic variants was not different between case and control pregnant women and was similar to with Hardy-Weinberg Equilibrium (HWE). However, in the younger subgroup (less than 35 years old), a significant difference was detected in allele and recessive model (p = 0.01). In the advanced age subgroup (more than or equal to 35 years old), G of MDM2 rs2279744 T > G revealed a significantly higher frequency in cases than controls (p = 0.045), and miR-34b/c rs4938723 T > C revealed a significant difference under the dominant model (p = 0.03), but no significant differences were observed in other models and in both younger and older subgroup (p > 0.05, respectively). These results suggest that individual polymorphisms were not associated with aneuploidy pregnancy, combined with age, they may serve as a risk factor for aneuploidy pregnancy.ConclusionCombination of TP53 rs1042522 G > C, MDM2 rs2279744 T > G, and miR-34b/c rs4938723 T > C polymorphisms with maternal age may be related to aneuploidy pregnancy susceptibility. These findings might elaborate on the genetic etiology of aneuploidy pregnancy.

Dataset Information

Interactions of miR-34b/c and TP53 polymorphisms on the risk of intracranial aneurysm.

Publications

Interactions of miR-34b/c and TP53 polymorphisms on the risk of intracranial aneurysm.

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