{"database":"biostudies-literature","file_versions":[],"scores":null,"additional":{"submitter":["Lin CH"],"funding":["Ministry of Science and Technology, Taiwan","Chang Gung Memorial Hospital"],"pagination":["e001416"],"full_dataset_link":["https://www.ebi.ac.uk/biostudies/studies/S-EPMC7938984"],"repository":["biostudies-literature"],"omics_type":["Unknown"],"volume":["9(1)"],"pubmed_abstract":["

Introduction

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.

Research design and methods

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.

Results

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 VTRNA2-1 in the training group. The methylation status of the VTRNA2-1 promoter was examined in the validation group via pyrosequencing reaction, and the hypomethylation of VTRNA2-1 (<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 VTRNA2-1 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 VTRNA2-1, 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 VTRNA2-1 promoter, the OR increased to 4.048 (95% CI 1.438 to 11.389, p=0.007).

Conclusions

The glycemic response to GLP-1 analog treatment is associated with the methylation status of the VTRNA2-1 promoter and polymorphism of rs2346018."],"journal":["BMJ open diabetes research & care"],"pubmed_title":["Methylation 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."],"pmcid":["PMC7938984"],"funding_grant_id":["MOST 105-2628-B-182-012- MY3","CORPG5F0011","MOST 109-2635-B-182-002","CMRPG3H0401, CMRPG3H0402,CMRPG3H0403","MOST 105-2628-B-182A-007-MY3","CMRPG3H0941, CMRPG3H0942,CMRPG3H0943","CMRPD1K0111"],"pubmed_authors":["Lee YS","Huang YY","Tsai CN","Lin CH"],"additional_accession":[]},"is_claimable":false,"name":"Methylation 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.","description":"

Introduction

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.

Research design and methods

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.

Results

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 VTRNA2-1 in the training group. The methylation status of the VTRNA2-1 promoter was examined in the validation group via pyrosequencing reaction, and the hypomethylation of VTRNA2-1 (<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 VTRNA2-1 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 VTRNA2-1, 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 VTRNA2-1 promoter, the OR increased to 4.048 (95% CI 1.438 to 11.389, p=0.007).

Conclusions

The glycemic response to GLP-1 analog treatment is associated with the methylation status of the VTRNA2-1 promoter and polymorphism of rs2346018.","dates":{"release":"2021-01-01T00:00:00Z","publication":"2021 Mar","modification":"2026-06-11T06:21:11.601Z","creation":"2024-11-21T10:22:00.397Z"},"accession":"S-EPMC7938984","cross_references":{"pubmed":["33674278"],"doi":["10.1136/bmjdrc-2020-001416"]}}