Role of telomeres and associated maintenance genes in Type 2 Diabetes Mellitus: A review

Sethi, Itty; Bhat, G. M.; Singh, Vinod; Kumar, Rakesh; Bhanwer, A.J.S.; Bamezai, R.; Sharma, Swarkar; Rai, Ekta

doi:10.1016/j.diabres.2016.10.015

Cited by 35 publications

(28 citation statements)

References 71 publications

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“…TERF2 is a component of shelterin complex and implicated in the formation and stability of T-loop 15 . The variant was reported to be associated with T2D in a candidate gene association study conducted in Caucasian women 16 .…”

Section: Resultsmentioning

confidence: 99%

“…Various functional studies have implicated telomere attrition in insulin resistance, impaired glucose tolerance, obesity, inflammation 12 as well as it has been found as an independent risk factor for T2D 13,14 . In fact, T2D and telomere attrition share common environmental risk factors including stress, less physical activity, and sedentary life style 15 . The telomere length is regulated and maintained by protein complexes (reviewed in Sethi et al, 2016) 15 .…”

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confidence: 99%

“…In fact, T2D and telomere attrition share common environmental risk factors including stress, less physical activity, and sedentary life style 15 . The telomere length is regulated and maintained by protein complexes (reviewed in Sethi et al, 2016) 15 . Few studies have indicated that the genes involved in the regulation of telomere length might also have implication in the telomere length attrition in T2D individuals [16][17][18][19][20] .…”

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confidence: 99%

“…With this background, the first case-control association study was performed to explore the role of telomere maintenance genes in the development of T2D in the North-west Indian population. Keeping account of potential functional implication of genes involved in telomere maintenance and regulation (reviewed in Sethi et al) 15 variants were selected in some of the genes from shelterin, CST (CTC1, STN1 and TEN1) and telomerase complex. The selected genes and their variant were Telomerase RNA component (TERC) -rs16847897, rs10936599, rs10936601, Telomerase Reverse Transcriptase (TERT) -rs2736100, Casein Kinase 2 subunit alpha 2 (CSNK2A2) -rs74019828, Telomeric Repeat Binding Factor 2 (TERF2) -rs4783704, Telomerase Associated Protein 1 (TEP1) -rs3093872, rs4982038, rs3093921, Telomeric Repeat Binding Factor 1 (TERF1) -rs2010441, rs6982126 and Oligonucleotide/Oligosaccharide-Binding Fold-Containing Protein 1 (OBFC1) -rs9419958 ( Supplementary Table S1).…”

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Telomere Maintenance Genes are associated with Type 2 Diabetes Susceptibility in Northwest Indian Population Group

Sethi

Sharma

et al. 2020

Sci Rep

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Telomere length attrition has been implicated in various complex disorders including Type 2 Diabetes (T2D). However, very few candidate gene association studies have been carried out worldwide targeting telomere maintenance genes. in the present study, variants in various critical telomere maintenance pathway genes for T2D susceptibility in Northwest Indian population were explored. With case-control candidate gene association study design, twelve variants from seven telomere maintenance genes were evaluated. Amongst these five variants, rs9419958 (OBFC1), rs4783704 (TERF2), rs16847897 (TERC/ LRRC31), rs10936599 (TERC/MYNN), and rs74019828 (CSNK2A2) showed significant association with T2D (at p-value ≤ 0.003, threshold set after Bonferroni correction) in the studied population. In silico analyses of these variants indicated interesting functional roles that warrant experimental validations. Findings showed that variants in telomere maintenance genes are associated with pathogenesis of T2D in Northwest Indian population. We anticipate further, such candidate gene association studies in other Indian populations and worldwide would contribute in understanding the missing heritability of T2D.

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Section: Resultsmentioning

confidence: 99%

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confidence: 99%

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Telomere Maintenance Genes are associated with Type 2 Diabetes Susceptibility in Northwest Indian Population Group

Sethi

Sharma

et al. 2020

Sci Rep

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“…Recent studies have found CSNK2A2 to be associated with relative leukocyte telomere length in South Asians. (66,67) RNF2 SAS Esophageal carcinoma is one of the most frequent malignant tumors and has been found to have high incidence rates in Asia. Studies have found RNF2 to be overexpressed in esophageal carcinoma tissues (68).…”

Section: Csnk2a2 Sasmentioning

confidence: 99%

Invariant Genes in Human Genomes

Ak²,

Brahmachari

2019

Preprint

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With large-scale human genome and exome sequencing, a lot of focus has gone in studying variations present in genomes and their associations to various diseases. Since major emphasis has been put on their variations, less focus has been given to invariant genes in the population.Here we present 60,706 genomes from the ExAC database to identify population specific invariant genes. Out of 1,336 total genes drawn from various population specific invariant genes, 423 were identified to be mostly (allele frequency less than 0.001) invariant across different populations. 46 of these invariant genes showed absolute invariance in all populations. Most of these common invariant genes have homologs in primates, rodents and placental mammals while 8 of them were unique to human genome and 3 genes still had unknown functions. Surprisingly, a majority were found to be X-linked and around 50% of these genes were not expressed in any tissues. The functional analysis showed that the invariant genes are not only involved in fundamental functions like transcription and translation but also in various developmental processes. The variations in many of these invariant genes were found to be associated with cancer, developmental diseases and dominant genetic disorders.

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Diabetes and Other Comorbidities: Microvascular and Macrovascular Diseases Diabetes and Cancer

Nithya

Sangavi

Srinithi

et al. 2023

Advances in Diabetes Research and Management

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Role of telomeres and associated maintenance genes in Type 2 Diabetes Mellitus: A review

Cited by 35 publications

References 71 publications

Telomere Maintenance Genes are associated with Type 2 Diabetes Susceptibility in Northwest Indian Population Group

Telomere Maintenance Genes are associated with Type 2 Diabetes Susceptibility in Northwest Indian Population Group

Invariant Genes in Human Genomes

Diabetes and Other Comorbidities: Microvascular and Macrovascular Diseases Diabetes and Cancer

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