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

Itty Sethi,Ekta Rai,Gh Rasool Bhat,Swarkar Sharma,A J S Bhanwer,Varun Sharma,Gurvinder Singh,Indu Sharma

doi:10.1038/s41598-020-63510-w

Itty Sethi, Ekta Rai + Show 6 more

Open Access

https://doi.org/10.1038/s41598-020-63510-w

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Abstract

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.

Highlights

Type 2 Diabetes (T2D) is a common progressive metabolic complex disorder, affecting 77 million individuals in India only[1]
India is a pivot of ethnicities and a foremost contributor to the world population with ample diversity yet least explored of all region especially lacking Genome wide association studies (GWAS) data for most of these population groups
The population enrolled in this study was genotyped for 12 Variants from 7 telomere maintenance genes including Oligosaccharide-Binding Fold-Containing Protein 1 (OBFC1), Telomeric Repeat Binding Factor 2 (TERF2), Casein Kinase 2 subunit alpha 2 (CSNK2A2), Telomerase Associated Protein 1 (TEP1), Telomerase Reverse Transcriptase (TERT), Telomerase RNA component (TERC) and Telomeric Repeat Binding Factor 1 (TERF1) described as in Supplementary Table S1

Summary

Introduction

Type 2 Diabetes (T2D) is a common progressive metabolic complex disorder, affecting 77 million individuals in India only[1]. Few studies have indicated that the genes involved in the regulation of telomere length might have implication in the telomere length attrition in T2D individuals[16,17,18,19,20]. Characteristic Age Gender - Male Gender - Female BMI-kg/m2 Systolic Blood Pressure (SBP)-mmHg Diastolic Blood Pressure (DBP)-mmHg Blood Glucose (Post Prandial)-mg/dl Triglycerides High Density Lipoproteins (HDL) Very Low Density Lipoprotein (VLDL) Cholesterol 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. 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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