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Epigenome-wide methylation study identified two novel CpGs associated with T2DM risk and a network of co-methylated CpGs capable of patient's classifications.
Giri, Anil K; Prasad, Gauri; Parekatt, Vaisak; Rajashekar, Donaka; Tandon, Nikhil; Bharadwaj, Dwaipayan.
Afiliação
  • Giri AK; Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi 110025, India.
  • Prasad G; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • Parekatt V; Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi 110025, India.
  • Rajashekar D; Academy of Scientific and Innovative Research (AcSIR), Ghaziabad 201002, India.
  • Tandon N; Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi 110025, India.
  • Bharadwaj D; Genomics and Molecular Medicine Unit, CSIR-Institute of Genomics and Integrative Biology, New Delhi 110025, India.
Hum Mol Genet ; 32(16): 2576-2586, 2023 08 07.
Article em En | MEDLINE | ID: mdl-37184252
ABSTRACT
Prevention of Type 2 diabetes mellitus (T2DM) pandemic needs markers that can precisely predict the disease risk in an individual. Alterations in DNA methylations due to exposure towards environmental risk factors are widely sought markers for T2DM risk prediction. To identify such individual DNA methylation signatures and their effect on disease risk, we performed an epigenome-wide association study (EWAS) in 844 Indian individuals of Indo-European origin. We identified and validated methylation alterations at two novel CpG sites in MIR1287 (cg01178710) and EDN2-SCMH1 (cg04673737) genes associated with T2DM risk at the epigenome-wide-significance-level (P < 1.2 × 10-7). Further, we also replicated the association of two known CpG sites in TXNIP, and CPT1A in the Indian population. With 535 EWAS significant CpGs (P < 1.2 × 10-7) identified in the discovery phase samples, we created a co-methylation network using weighted correlation network analysis and identified four modules among the CpGs. We observed that methylation of one of the module associates with T2DM risk factors (e.g. BMI, insulin and C-peptide) and can be used as markers to segregate T2DM patients with good glycemic control (e.g. low HbA1c) and dyslipidemia (low HDL and high TG) from the other patients. Additionally, an intronic SNP (rs6503650) in the JUP gene, a member of the same module, associated with methylation at all the 14 hub CpG sites of that module as methQTL. Our network-assisted EWAS is the first to systematically explore DNA methylation variations conferring risks to T2DM in Indians and use the identified risk CpG sites for patient segregation with different clinical outcomes. These findings can be useful for better stratification of patients to improve the clinical management and treatment effects.
Assuntos

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs / Diabetes Mellitus Tipo 2 Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Hum Mol Genet Assunto da revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Índia

Texto completo: 1 Coleções: 01-internacional Base de dados: MEDLINE Assunto principal: MicroRNAs / Diabetes Mellitus Tipo 2 Tipo de estudo: Etiology_studies / Prognostic_studies / Risk_factors_studies Limite: Humans Idioma: En Revista: Hum Mol Genet Assunto da revista: BIOLOGIA MOLECULAR / GENETICA MEDICA Ano de publicação: 2023 Tipo de documento: Article País de afiliação: Índia