ENAapplication/xmlftp.sra.ebi.ac.uk/vol1/fastq/SRR120/042/SRR12096042/SRR12096042.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR120/033/SRR12096033/SRR12096033.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR120/027/SRR12096027/SRR12096027.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR120/032/SRR12096032/SRR12096032.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR120/034/SRR12096034/SRR12096034.fastq.gzftp.sra.ebi.ac.uk/vol1/fastq/SRR120/035/SRR12096035/SRR12096035.fastq.gzprimaryOK200GenomicsBiotechnology, Manipal School of Life Sciences, Manipal Academy of Higher Educationhttps://www.ebi.ac.uk/ena/browser/view/PRJNA642130Homo sapiensAims: Metformin is a widely used, primary drug of choice to treat individuals with type 2 diabetes (T2D). Clinically, inter-individual variability of drug response is of significant concern. The targets and precise mechanisms of action for metformin is still under interrogation. In the present study, a whole transcriptome analysis was performed with an intent to identify predictive biomarkers of metformin response in T2D individuals. Methods: Twenty drug naïve individuals with T2D and ten healthy controls were enrolled. T2D individuals were administrated with metformin monotherapy and were defined as responders and non-responders based on the changes in their glycated haemoglobin (HbA1c) over a period of three months. Poly(A) RNA Seq was performed using Ion Torrent Proton platform and differentially expressed genes were identified from the transcriptome profiles. The gene prioritization, enrichment analysis, drug-gene interactions, disease gene association analysis were performed using various tools and databases. A correlation analysis was also performed between gene expression and change in HbA1c levels after 3 months of metformin therapy. Results: The expression analysis highlighted differentially expressed genes in metformin responders, non-responders and healthy individuals. The gene prioritization and enrichment analysis highlighted potential targets for predicting metformin response (n=35) as well as T2D disease (n=14). The drug-gene interactions did not show any direct association with diabetes drugs. However, the expression of GDF15, TWISTNB and RPL36A genes showed maximum correlation with change in HbA1c levels after 3 months of metformin therapy. The disease gene association analysis highlighted rs113805659 in MAGI2 gene to be linked with T2D in African Americans. Conclusion: The results of the present study provide evidence for the perturbed transcriptome and pathways associated with metformin drug response in T2D individuals. Overall design: Whole transcriptome profile of 20 drug naïve individuals with T2D and 10 healthy controls was generated for total RNA isolated from whole blood using Ion Torrent ProtonENAtype 2, LA-6023, dimethyldiguanide, Materials, maturity-onset diabetes, adult onset diabetes, determination, Transcriptome Profile, noninsulin-dependent diabetes mellitus, Metformin Hydrochloride, Gene Expression Profile, Gene, N(1), Profiles, noninsulin dependent diabetes, Dimethylguanylguanidine, Non-Insulin Dependent Diabetes Mellitus, 1, 2, non-insulin-dependent diabetes mellitus, Imidodicarbonimidic diamide, noninsulin-dependent, reactivity, type II diabetes mellitus, Genetic, non-insulin dependent diabetes, N-dimethylbiguanide, Profile, N, 1-dimethylbiguanide, non-insulin dependent diabetes mellitus, type 2 diabetes mellitus, Signatures, Dimethylbiguanidine, NIDDM, adult-onset diabetes, N(1)-dimethylbiguanide, drugs, type 2 diabetes mellitus non-insulin dependent, LA 6023, N-dimethylimidodicarbonimidic diamide, metformin, Expression Signature, medicine, Transcriptomes, Metformin HCl, type 2 diabetes, severe, association with, diabetes, diabetes mellitis type II, Transcriptome, drug, Expression Profiles, T2DM - type 2 diabetes mellitus, N-dimethylguanylguanidine, responsivity., late onset, Cistrons, Gene Expression, N-dimethyl-, metformine, Expression Signatures, Gene Expression Signatures, chemical analysis, Hydrochloride, Genetic Materials, Gene Expression Signature, Expression Profile, Metformin, Genetic Material, metforminum, Transcriptome Profiles, dimethylbiguanide, Type 2 Diabetes, diabetes mellitus, susceptibility to, metformina, HCl, Type II Diabetes, N-dimethyldiguanide, insulin resistance, insulin resistance-related, diabetes mellitis type 2, type II, non-insulin-dependent, Material, Gene Expression Profiles, type II diabetes, N-dimethyltriimidodicarbonic diamide, protection against, digenic, Cistron, assay, response, Signature, hypertension, Glucophagetype 2, LA-6023, dimethyldiguanide, Materials, maturity-onset diabetes, adult onset diabetes, determination, Transcriptome Profile, noninsulin-dependent diabetes mellitus, Metformin Hydrochloride, Gene Expression Profile, Gene, N(1), Profiles, noninsulin dependent diabetes, Dimethylguanylguanidine, Non-Insulin Dependent Diabetes Mellitus, 1, 2, non-insulin-dependent diabetes mellitus, Imidodicarbonimidic diamide, noninsulin-dependent, reactivity, type II diabetes mellitus, Genetic, non-insulin dependent diabetes, N-dimethylbiguanide, Profile, N, 1-dimethylbiguanide, non-insulin dependent diabetes mellitus, type 2 diabetes mellitus, Signatures, Dimethylbiguanidine, NIDDM, adult-onset diabetes, N(1)-dimethylbiguanide, drugs, type 2 diabetes mellitus non-insulin dependent, LA 6023, N-dimethylimidodicarbonimidic diamide, metformin, Expression Signature, medicine, Transcriptomes, Metformin HCl, type 2 diabetes, severe, association with, diabetes, diabetes mellitis type II, Transcriptome, drug, Expression Profiles, T2DM - type 2 diabetes mellitus, N-dimethylguanylguanidine, responsivity., late onset, Cistrons, Gene Expression, N-dimethyl-, metformine, Expression Signatures, Gene Expression Signatures, chemical analysis, Hydrochloride, Genetic Materials, Gene Expression Signature, Expression Profile, Metformin, Genetic Material, metforminum, Transcriptome Profiles, dimethylbiguanide, Type 2 Diabetes, diabetes mellitus, susceptibility to, metformina, HCl, Type II Diabetes, N-dimethyldiguanide, insulin resistance, insulin resistance-related, diabetes mellitis type 2, type II, non-insulin-dependent, Material, Gene Expression Profiles, type II diabetes, N-dimethyltriimidodicarbonic diamide, protection against, digenic, Cistron, assay, response, Signature, hypertension, Glucophage0.00.00.00.00.0falseTranscriptome analysis of Newly Diagnosed Type 2 Diabetes Subjects identifies genes to predict Metformin drug ResponseTranscriptome analysis of Newly Diagnosed Type 2 Diabetes Subjects identifies genes to predict Metformin drug Response2022-07-062022-07-06PRJNA642130GSE1533159606