biostudies-literatureLin CHMinistry of Science and Technology, TaiwanChang Gung Memorial Hospitale001416https://www.ebi.ac.uk/biostudies/studies/S-EPMC7938984biostudies-literatureUnknown9(1)<h4>Introduction</h4>Therapeutic efficiency of glucagon-like peptide-1 (GLP-1) analog is about 50%-70% in type 2 diabetes mellitus (T2DM). Discovery of potential genetic biomarkers for prediction of treatment efficiency of GLP-1 analog before therapy is still necessary. We assess whether DNA methylation was associated with glycemic response to GLP-1 analog therapy in patients with poorly controlled T2DM.<h4>Research design and methods</h4>Genomic DNA was extracted from the peripheral blood of training (n=10) and validation (n=128) groups of patients with T2DM receiving GLP-1 analogs. DNA methylome was analyzed using Infinium Human Methylation EPIC Bead Chip in the training group. The candidate genes were examined using a pyrosequencing platform in the validation group. The association between DNA methylation status and glycemic response to GLP-1 was analyzed in these patients.<h4>Results</h4>The most differential methylation region between those with a good (responsive) and poor (unresponsive) glycemic response to GLP-1 analog therapy was located on chromosome 5q31.1 (135415693 to 135416613), the promoter of <i>VTRNA2-1</i> in the training group. The methylation status of the <i>VTRNA2-1</i> promoter was examined in the validation group via pyrosequencing reaction, and the hypomethylation of <i>VTRNA2-1</i> (<40% methylation) was significantly associated with poor glycemic response to GLP-1 treatment (OR 2.757, 95% CI 1.240 to 6.130, p=0.011). Since the <i>VTRNA2-1</i> promoter region was previously reported maternal imprinting extended to the adjacent centromeric CCCTC-binding factor site that contained an A/C polymorphism (rs2346018), which was associated with methylation density of <i>VTRNA2-1</i>, this A/C polymorphism was also integrated to analyze association with glycemic response to GLP-1 analog therapy. In patients with the A allele of rs2346018 and hypomethylation (<40%) on the <i>VTRNA2-1</i> promoter, the OR increased to 4.048 (95% CI 1.438 to 11.389, p=0.007).<h4>Conclusions</h4>The glycemic response to GLP-1 analog treatment is associated with the methylation status of the <i>VTRNA2-1</i> promoter and polymorphism of rs2346018.BMJ open diabetes research & careMethylation status of vault RNA 2-1 promoter is a predictor of glycemic response to glucagon-like peptide-1 analog therapy in type 2 diabetes mellitus.PMC7938984MOST 105-2628-B-182-012- MY3CORPG5F0011MOST 109-2635-B-182-002CMRPG3H0401, CMRPG3H0402,CMRPG3H0403MOST 105-2628-B-182A-007-MY3CMRPG3H0941, CMRPG3H0942,CMRPG3H0943CMRPD1K0111Lee YSHuang YYTsai CNLin CHfalseMethylation status of vault RNA 2-1 promoter is a predictor of glycemic response to glucagon-like peptide-1 analog therapy in type 2 diabetes mellitus.<h4>Introduction</h4>Therapeutic efficiency of glucagon-like peptide-1 (GLP-1) analog is about 50%-70% in type 2 diabetes mellitus (T2DM). Discovery of potential genetic biomarkers for prediction of treatment efficiency of GLP-1 analog before therapy is still necessary. We assess whether DNA methylation was associated with glycemic response to GLP-1 analog therapy in patients with poorly controlled T2DM.<h4>Research design and methods</h4>Genomic DNA was extracted from the peripheral blood of training (n=10) and validation (n=128) groups of patients with T2DM receiving GLP-1 analogs. DNA methylome was analyzed using Infinium Human Methylation EPIC Bead Chip in the training group. The candidate genes were examined using a pyrosequencing platform in the validation group. The association between DNA methylation status and glycemic response to GLP-1 was analyzed in these patients.<h4>Results</h4>The most differential methylation region between those with a good (responsive) and poor (unresponsive) glycemic response to GLP-1 analog therapy was located on chromosome 5q31.1 (135415693 to 135416613), the promoter of <i>VTRNA2-1</i> in the training group. The methylation status of the <i>VTRNA2-1</i> promoter was examined in the validation group via pyrosequencing reaction, and the hypomethylation of <i>VTRNA2-1</i> (<40% methylation) was significantly associated with poor glycemic response to GLP-1 treatment (OR 2.757, 95% CI 1.240 to 6.130, p=0.011). Since the <i>VTRNA2-1</i> promoter region was previously reported maternal imprinting extended to the adjacent centromeric CCCTC-binding factor site that contained an A/C polymorphism (rs2346018), which was associated with methylation density of <i>VTRNA2-1</i>, this A/C polymorphism was also integrated to analyze association with glycemic response to GLP-1 analog therapy. In patients with the A allele of rs2346018 and hypomethylation (<40%) on the <i>VTRNA2-1</i> promoter, the OR increased to 4.048 (95% CI 1.438 to 11.389, p=0.007).<h4>Conclusions</h4>The glycemic response to GLP-1 analog treatment is associated with the methylation status of the <i>VTRNA2-1</i> promoter and polymorphism of rs2346018.2021-01-01T00:00:00Z2021 Mar2026-06-11T06:21:11.601Z2024-11-21T10:22:00.397ZS-EPMC79389843367427810.1136/bmjdrc-2020-001416