Cluster-specific genetic associations of CDKAL1, CDKN2A, CDKN2B, HHEX, KCNQ1, MTNR1B, PAX4, SLC30A8, TCF7L2, and UBE2E2 variants in new onset type 2 diabetes.

Nattachet Plengvidhya, Nipaporn Teerawattanapong, Tassanee Narkdontr, Saranya Innang, Suavaluk Songlilitchuwong, Sarocha Suthon, Watip Tangjittipokin

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Article in Scientific reports, 2025. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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7 authors.

Nattachet PlengvidhyaDivision of Endocrinology and Metabolism, Department of Medicine, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Nipaporn TeerawattanapongSiriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Tassanee NarkdontrSiriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Saranya InnangSiriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Suavaluk SonglilitchuwongSiriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Sarocha SuthonSiriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand.

Watip TangjittipokinSiriraj Center of Research Excellence for Diabetes and Obesity (SiCORE-DO), Research Department, Faculty of Medicine Siriraj Hospital, Mahidol University, Bangkok, Thailand. watip.tan@mahidol.edu.

Funding

Mahidol University (Fundamental Fund: fiscal year 2023 by National Science Research and Innovation Fund (NSRF)) FF-028/2566

6 · The paper itself

Abstract

Type 2 diabetes (T2D) is a heterogeneous metabolic disorder. Recent cluster-based classifications offer insights into distinct pathophysiological subtypes. The objective of the study is to investigate the association of genetic variants in T2D-related genes with defined T2D clusters. We analyzed 678 single nucleotide polymorphisms (SNPs) from ten genes (CDKAL1, CDKN2A, CDKN2B, HHEX, KCNQ1, MTNR1B, PAX4, SLC30A8, TCF7L2, and UBE2E2) in 471 T2D patients classified into four clusters: Severe Insulin-Deficient Diabetes (SIDD), Mild Obesity-related Diabetes (MOD), Mild Age-related Diabetes (MARD), and Metabolic Syndrome-related Diabetes (MSD). Genotyping was performed using the Axiom PDMRAv2 array. Following Hardy-Weinberg Equilibrium filtering, 376 SNPs were analysed. The association between T2D clusters and SNPs was assessed by multinomial logistic regression. Nineteen SNPs showed significant differences in genotypic frequencies among clusters (p < 0.05). Eight SNPs (rs61875103 in TCF7L2; rs12576156, rs2283220, rs2074197, and rs163165 KCNQ1; rs4710943, rs9368248, and rs6456379 in CDKAL1) significantly associated with cluster assignment. Cluster-specific effects were most notable in SIDD and MOD subgroups. Our findings support genetic heterogeneity of TCF7L2, KCNQ1, and CDKAL1 in T2D clusters and underscore the potential for genetically informed precision therapy strategies.

Indexed as

Diabetes Mellitus, Type 2Polymorphism, Single NucleotideAdultAgedCyclin-Dependent Kinase 5Cyclin-Dependent Kinase Inhibitor p15Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18FemaleGenetic Association StudiesGenetic Predisposition to DiseaseGenotypeHomeodomain ProteinsHumansKCNQ1 Potassium ChannelMaleCDKAL1 protein, humanCDKN2A protein, humanCDKN2B protein, humanCyclin-Dependent Kinase 5Cyclin-Dependent Kinase Inhibitor p15Cyclin-Dependent Kinase Inhibitor p16Cyclin-Dependent Kinase Inhibitor p18HHEX protein, humanHomeodomain ProteinsKCNQ1 Potassium ChannelKCNQ1 protein, humanMTNR1B protein, humanPaired Box Transcription FactorsPAX4 protein, humanReceptor, Melatonin, MT2SLC30A8 protein, humanTCF7L2 protein, humanTranscription Factor 7-Like 2 ProteinTranscription FactorstRNA MethyltransferasesUBE2E2 protein, humanUbiquitin-Conjugating EnzymesZinc Transporter 8Axiom arrayClustersGenetic associationPrecision medicineSNPType 2 diabetes

Identifiers

PMID41422334

DOI10.1038/s41598-025-32840-y

PMCPMC12830632

What Socratic holds

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LicenceCC BY

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.