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Polymorphisms in lipid metabolism related miRNA binding sites and risk of metabolic syndrome
1Department of Epidemiology and Biostatistics, School of Public Health, Nanjing Medical University, Nanjing, Jiangsu, China.
Abstract:
MicroRNAs (miRNAs) regulate posttranscriptional gene expression usually by binding to 3'-untranslated regions (3'UTRs) of target message RNAs (mRNAs). Previous studies have demonstrated that SNPs within miRNA target sites could modulate miRNA-mRNA interaction to affect the regulation of target genes and the individual's diseases. So far, little is known about the relationship of miRNA binding site polymorphisms with the risk of metabolic syndrome (MetS) in the general population. Therefore, we conducted a case-control study in Chinese Han population to evaluate the association between SNPs within miRNA binding sites and risk of MetS. 8 SNPs in miRNA binding sites with a minor allele frequency (MAF) of ≥ 0.05 in the Chinese Han population were selected by bioinformatics software. TaqMan ®assay was performed to test the genotypes in MetS patients (n=1026) and normal controls (n=1032). We found rs5750146 (adjusted odds ratio (OR)=1.24 for GA/AA, P=0.023, compared with GG), rs5999924 (adjusted OR=1.22 for AT/TT, P=0.038, compared with AA) in the APOL6 3'UTR were identified to correlate with MetS in the total sample and females. Rs11724758 (adjusted OR=0.65 for AA, P=0.002, compared with GG) in the FABP2 3'UTR was found to correlate with MetS in the total sample and males. Correlations between FABP2 rs11724758 polymorphisms and components of MetS reveal that high-density lipoprotein cholesterol (HDL-c) levels are significantly higher in FABP2 rs11724758 AA genotype carrier compared with noncarriers, whereas triglycerides (TG) and fasting plasma glucose (FG) were to be significantly lower in the AA genotype carrier. These findings indicate that these three polymorphisms which located at the predicted miRNAs binding sites were identified to contribute to susceptibility to MetS in the Chinese Han population.
Insights
Single nucleotide polymorphisms (SNPs) in microRNA (miRNA) binding sites are associated with metabolic syndrome (MetS) risk. Specific SNPs in APOL6 and FABP2 genes impact MetS development and its components in the Chinese Han population.
Area of Science:
- Genetics
- Molecular Biology
- Metabolic Diseases
Background:
- MicroRNAs (miRNAs) regulate gene expression posttranscriptionally, often by interacting with 3'-untranslated regions (3'UTRs) of messenger RNAs (mRNAs).
- Single nucleotide polymorphisms (SNPs) within miRNA binding sites can alter miRNA-mRNA interactions, influencing gene regulation and disease susceptibility.
- The association between miRNA binding site polymorphisms and the risk of metabolic syndrome (MetS) remains largely unexplored in general populations.
Purpose of the Study:
- To investigate the relationship between SNPs in miRNA binding sites and the risk of developing metabolic syndrome (MetS).
- To evaluate the association of specific miRNA binding site polymorphisms with MetS and its clinical components in the Chinese Han population.
Main Methods:
- A case-control study was conducted involving 1026 MetS patients and 1032 healthy controls from the Chinese Han population.
- Bioinformatics software identified 8 SNPs in miRNA binding sites with a minor allele frequency (MAF) of ≥ 0.05.
- Genotyping was performed using TaqMan® assay for the selected SNPs.
Main Results:
- Two SNPs in the APOL6 3'UTR (rs5750146 and rs5999924) were significantly associated with MetS risk in the total sample and in females.
- One SNP in the FABP2 3'UTR (rs11724758) was significantly associated with MetS risk in the total sample and in males.
- FABP2 rs11724758 polymorphism correlated with MetS components, showing higher high-density lipoprotein cholesterol (HDL-c) and lower triglycerides (TG) and fasting plasma glucose (FG) in AA genotype carriers.
Conclusions:
- Three identified polymorphisms in predicted miRNA binding sites contribute to susceptibility to metabolic syndrome (MetS) in the Chinese Han population.
- These genetic variations may serve as potential biomarkers for MetS risk and its associated metabolic dysregulations.
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