Polymorphisms in lipid metabolism related miRNA binding sites and risk of metabolic syndrome

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.

Keywords: 3’UTRs; 3’untranslated regions; AHA; American Heart Association; BMI; Body Mass Index; CI; Confidence Interval; DBP; FPG; Fasting plasma glucose; HDL-C; Haplotype; High density lipoprotein cholesterin; IDF; International Diabetes Federation; LDA; LDL-C; Linkage Disequilibrium Analysis; Low density lipoprotein cholesterin; MAF; MetS; Metabolic Syndrome; Metabolic syndrome; NCBI; NHLBI; National Center of Biotechnology Information; National Heart, Lung and Blood Institute; OR; Odds Ratio; PCR; Polymerase Chain Reaction; SBP; SNP; Single Nucleotide Polymorphism; Single nucleotide polymorphism; T2DM; TC; TG; Total cholesterol; Triglyceride; Type 2 diabetes mellitus; WC; diastolic blood pressure; mRISC; miRNA; miRNA target binding sites; miRNA-induced silencing effector complex; microRNA; minor allele frequency; systolic blood pressure; waist circumference.