Mining of single nucleotide polymorphisms in the 3' untranslated region of liver cancer-implicated miR-122 target genes

The Myostatin (MSTN), or Growth and Differentiation Factor 8 (GDF8), gene has been implicated in the double muscling phenomenon, in which a series of mutations render the gene inactive and unable to properly regulate muscle fibre deposition. Single nucleotide polymorphisms (SNPs) in the MSTN gene have been correlated to production traits, making it a candidate target gene to enhance livestock and fowl productivity. This study aimed to assess any association of three SNPs in the rabbit MSTN gene (c.713T>A in exon 2, c.747+34C>T in intron 2, and c.*194A>G in 3’-untranslated region) and their combinations, with carcass, production and reproductive traits. The investigated traits included individual body weight, daily body weight gain, carcass traits and reproductive traits. The 3 SNPs were screened using PCR-restriction fragment length polymorphism (RFLP)-based analysis and the effects of the different SNP genotypes and their combinations were estimated in a rabbit population. Additionally, additive and dominance effects were estimated for significant traits. The results found no significant association between the c.713 T>A SNP and all the examined traits. Allele T at the c.747+34C>T SNP was only significantly associated (P<0.05) with increased body weight at 12 wk of age. However, for the SNP residing in the 3’ untranslated region (c.*194A>G), allele G was significantly associated (P<0.05) with increased body weight and high growth rate. Genotype GG at the c.*194A>G SNP also had positive effects on most carcass traits. The estimated additive genetic effect for the c.*194A>G SNP was significant (P<0.05) with most body weight, daily gain and carcass traits. No significant association was obtained between any MSTN SNPs and reproductive traits. In the combinations analysis, regardless of the genotypes of SNPs at c.713T>A and c.747+34C>T, GG at the c.*194A>G SNP correlated with highest values in body weight and daily weight gain. In conclusion, the ‘G’ allele at the c.*194A>G SNP had positive effects on growth and carcass traits and so could be used as a favourable allele in planning rabbit selection. Further population-wide studies are necessary to test the association of the c.*194A>G SNP with carcass traits. We also recommend evaluation of the potential effects of the c.*194A>G SNP on MSTN gene expression.

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Investigating Single Nucleotide Polymorphisms In MiRNA-Binding Sites In The K-RAS 3' Untranslated Region As A Novel Biomarker For Lung Cancer

10.1164/ajrccm-conference.2012.185.1_meetingabstracts.a6349 ◽

2012 ◽

Author(s):

Connie E. Kim ◽

Kam-Meng Tchou-Wong ◽

William Rom

Keyword(s):

Lung Cancer ◽

Single Nucleotide Polymorphisms ◽

Binding Sites ◽

Untranslated Region ◽

Nucleotide Polymorphisms ◽

Single Nucleotide

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Molecular Screening and Association Analyses of the Interleukin 6 Receptor Gene Variants with Type 2 Diabetes, Diabetic Nephropathy, and Insulin Sensitivity

The Journal of Clinical Endocrinology & Metabolism ◽

10.1210/jc.2004-1606 ◽

2005 ◽

Vol 90 (2) ◽

pp. 1123-1129 ◽

Cited By ~ 41

Author(s):

Hua Wang ◽

Zhengxian Zhang ◽

Winston Chu ◽

Terri Hale ◽

Judith J. Cooper ◽

...

Keyword(s):

Type 2 Diabetes ◽

Diabetic Nephropathy ◽

Insulin Sensitivity ◽

Single Nucleotide Polymorphisms ◽

Untranslated Region ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Northern European ◽

A Minor

IL-6 levels and polymorphisms have been implicated in type 2 diabetes mellitus (T2DM) and insulin resistance. The IL-6 receptor (IL-6R) comprises two subunits, IL-6R and gp130, of which IL-6R confers specificity to IL-6 action and is located in a region of replicated linkage to T2DM on chromosome 1q21. We screened this gene for variation in Northern European Caucasian and African-American ethnic groups. We identified 11 variants with a minor allele frequency over 5%, including two amino acid changes (D358A and V385I) and four variants in the 3′ untranslated region. No variant was associated with obesity or measures of insulin sensitivity, but two single nucleotide polymorphisms in the 3′ untranslated region showed a trend to an association with T2DM in all Caucasians, and three single nucleotide polymorphisms, including D358A, showed a trend (P < 0.06) to an association with T2DM among the subset of Northern European Caucasians. Variant V385I was unique to African-Americans and was significantly associated with diabetes and diabetic nephropathy (P < 0.05). Among individuals heterozygous for the four variants in the transcribed sequence, one allele was significantly overrepresented, thus suggesting the existence of a regulatory variant controlling mRNA stability or expression. IL-6R is not likely to explain the linkage to diabetes in this region, but our work supports a minor role of variants in T2DM risk and suggests that sequence variants may alter IL-6R mRNA levels and possibly levels of soluble IL-6R.

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Single Nucleotide Polymorphisms inmiR-122Are Associated with the Risk of Hepatocellular Carcinoma in a Southern Chinese Population

BioMed Research International ◽

10.1155/2018/1540201 ◽

2018 ◽

Vol 2018 ◽

pp. 1-6 ◽

Cited By ~ 4

Author(s):

Chunhua Bei ◽

Shun Liu ◽

Xiangyuan Yu ◽

Moqin Qiu ◽

Bo Tang ◽

...

Keyword(s):

Hepatocellular Carcinoma ◽

Single Nucleotide Polymorphisms ◽

Chinese Population ◽

Target Genes ◽

Risk Group ◽

High Risk Group ◽

Nucleotide Polymorphisms ◽

Single Nucleotide ◽

Southern Chinese ◽

Increased Risk

Single nucleotide polymorphisms (SNPs) in microRNA may affect its expression and regulation of target genes, which may consequently alter individual susceptibility to cancer. In this study we aimed to investigate associations betweenmiR-122polymorphisms and hepatocellular carcinoma (HCC) in a southern Chinese population. Three selected SNPs inmiR-122(rs9966765, rs1135519, and rs17669) were genotyped in 1050 HCC patients and 1079 cancer-free controls using Sequenom MassARRAY platform and the associations of the three SNPs and HCC risk were evaluated. We found that individuals with the rs1135519 CC genotypes had a significant increased risk of HCC than those with TT genotypes (adjusted OR=2.71, 95% CI=1.15-6.36, andP=0.022), while the rs9966765 CC genotypes showed a borderline significant association with increased risk of HCC when compared with the GG genotypes (adjusted OR=2.38, 95% CI=0.99-5.75, andP=0.052). There was also a significant increased risk of HCC when combining risk genotypes of these loci, i.e., rs1135519 CC and rs9966765 CC. Compared with the low-risk group (0 risk genotype), the high risk group (1-2 risk genotypes) had significantly increased risk of HCC (OR=1.61, 95% CI=1.05-2.44, andP=0.028). Further genotype-expression analysis revealed that cases carrying the CC genotype of rs1135519 had lower levels ofmiR-122expression than those with the TT genotype. Our results suggest that SNP of rs1135519 modulatesmiR-122expression and contributes to the genetic susceptibility of HCC, either independently or together with rs9966765 inmiR-122.Further well-designed studies with lager sample sizes are needed to confirm our findings.

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