Association of the 3'UTR FOXO3a Polymorphism rs4946936 with an Increased Risk of Childhood Acute Lymphoblastic Leukemia in a Chinese Population

Self Cite

Background/Aims: IGF1 is a key regulator in cell proliferation and apoptosis, and the 3' un-translated region (3'UTR) of the gene plays an important role in gene expression. For the first time, we explored the relationship between polymorphisms in the IGF1 3'UTR region and the risk of childhood acute lymphoblastic leukemia (ALL). Methods: Questionnaires were applied to collect epidemiological data. The genotypes of IGF1 polymorphisms were tested in a population of 744 ALL patients and 1088 cancer-free controls utilizing Taqman. Cell functional studies included real-time PCR, cell culture and transfection and luciferase assays. Results: We found that rs6214 homozygous AA genotype and rs6218 homozygous CC genotype were significantly associated with increased risk of childhood ALL. In addition, rs6218 CC genotype was associated with increased level of IGF1 mRNA in bone marrow, and the mutation in rs6218 led to aberrant binding capacity of hsa-miR-603 and hsa-miR-3941 in the 3'UTR of IGF1. Conclusion: Polymorphisms of rs6214 and rs6218 in the 3'UTR of IGF1 are associated with childhood ALL susceptibility, and the polymorphism of rs6218 is related with IGF1 expression at mRNA level.

Section: Introductionmentioning

confidence: 99%

Interaction Between IGF1 Polymorphisms and the Risk of Acute Lymphoblastic Leukemia in Chinese Children

Lu¹,

Wang²,

He³

et al. 2015

Self Cite

“…There is accumulating evidence demonstrating that SNPs localized at miRNA binding sites (miRSNPs) could affect the binding of miRNAs to the target genes and in turn result in reduction or increase in translation of the target mRNA and altered susceptibility to cancer [28, 32]. For example, previous studies showed that the rs2910164 polymorphism harboring the sequence for miR-146a could influence susceptibility to gastric cancer in a Chinese population, while rs4143815 and rs4819388 SNPs in the 3'-UTR of B7-H1 and B7-H2 genes, respectively, associated with development of gastric cancer [33-35].…”

Section: Discussionmentioning

confidence: 99%

“…Briefly, genomic DNA samples of 10 ng each were amplified using PCR in a total volume of 5 µL containing TaqMan Universal Master Mix, 80x SNP Genotyping AssayMix, DNase-free water and 10-ng DNA. The PCR conditions were 50 °C for 2 min and then 95 °C for 10 min, followed by 40 cycles of 95 °C for 15 s and 60 °C for 1 min in a 384-well ABI 7900HT Real Time PCR System as described previously [28]. …”

Section: Methodsmentioning

confidence: 99%

Methylene Tetrahydrofolate Reductase (MTHFR) rs868014 Polymorphism Regulated by miR-1203 Associates with Risk and Short Term Outcome of Ischemic Stroke

et al. 2017

Background/Aims: Genetic polymorphisms of methylene tetrahydrofolate reductase (MTHFR) were associated with ischemic stroke risk. This study analyzed MTHFR polymorphisms at the 3'-untranslated region for association with risk and outcome of ischemic stroke in a Chinese Han population. Methods: 500 patients and 600 healthy volunteers were enrolled for MTHFR rs868014 genotyping identified bioinformatically. The binding of miR-1203 to MTHFR rs868014 was determined by luciferase assay, MTHFR expression was assessed using qRT-PCR, and plasma homocysteine levels were assayed by ELISA. Results: Cigarette smoking, alcohol consumption, diabetes, hypertension (all P <0.001), low levels of serum high-density lipoprotein-C (P = 0.01), and high levels of serum low-density lipoprotein-C (P = 0.005) were associated with an increased risk of developing ischemic stroke. BMI and total serum cholesterol concentration was not associated with ischemic stroke. MTHFR rs868014 TC and CC genotypes were significantly associated with increased risk of ischemic stroke compared with the TT genotype (OR: 1.52; 95% CI: 1.01-3.39 for TC genotype, while OR: 1.99; 95% CI: 1.29-3.88 for CC genotype). Furthermore, the MTHFR rs868014 SNP was associated with a poor short-term ischemic stroke outcome. qRT-PCR confirmed that MTHFR rs868014 TC or CC genotypes could facilitate miR-1203 binding leading to low MTHFR levels in cells. In addition, patients carrying the MTHFR rs868014 TC or CC genotypes were associated with accumulation of serum tHcy and a poor ischemic stroke outcome. Linkage disequilibrium analysis indicated that the newly identified SNP rs868014 was strongly linked with the MTHFR A1298C polymorphism. Conclusion: This study demonstrates that the MTHFR rs868014 SNP is associated with increased risk in developing ischemic stroke, miR-1203 binding, low MTHFR levels in cells, and poor shot term outcome of patients.

“…Currently, miRNA has been documented as function factor involved in the SNP associated post-transcriptional regulation [4, 5]. The binding of certain miRNA could be influenced in different genotypes causing the different expression of mRNA level with [6, 7].…”

Section: Introductionmentioning

confidence: 99%

The SNP Rs915014 in MTHFR Regulated by MiRNA Associates with Atherosclerosis

Xin-ye

Wang

Chi

et al. 2018

Background/Aims: The association between the genetic polymorphisms located in either the exon or untranslated region of MTHFR and the risk of human atherosclerosis has been well-documented. This study analyzed MTHFR polymorphisms at the 3’-untranslated region for association with risk and outcome of atherosclerosis in a Chinese Han population. Methods: The hospital based case-control study was conducted with 500 patients and 600 healthy volunteers as control enrolled. The genotyping was conducted by using Taqman probe. The potential interaction was predicted by multiple bioinformatics analysis. The relative expression of MTHFR was detected by qRT-PCR. Further confirmation was determined by dual-luciferase assay. The plasma homocysteine levels were assayed by ELISA. Results: Cigarette smoking, alcohol consumption, diabetes, hypertension and low levels of serum high-density lipoprotein-C were associated with an increased risk of developing ischemic stroke. MTHFR rs915014 AG and GG genotypes were significantly associated with increased risk of rs915014 compared with the GG genotype. The qRT-PCR confirmed that MTHFR rs915014 AG or GG genotypes could facilitate miR-2861 binding leading to decreased MTHFR levels in cells. In addition, patients carrying the MTHFR rs915014 AG or GG genotypes were associated with accumulation of circulating tHcy volume and a poor atherosclerosis consequence. Conclusions: This study demonstrates that the MTHFR rs915014 is associated with increased risk of atherosclerosis and might be a shot term outcome biomarker for atherosclerosis patients.