Human Telomerase Reverse Transcriptase and Metallothionein 1A Expressions in Relation with Telomere Length in Healthy Individuals

Abstract

Introduction: Telomere length (TL), the marker of cellular aging, is regulated by a reverse transcriptase complex that contains reverse transcriptase (hTERT). Oxidative stress (OS) generated by environmental and genetic reasons can alter the TL in the blood. Metallothionein (MT) is a metal-binding protein with a low molecular weight and a high cysteine content found in all eukaryotes. Studies using animal models have provided evidence supporting the antioxidant function of MT. Since TL and MT both can be altered by oxidative stress, the present study was conducted to find association between them. Methodology: A total of 40 healthy volunteers in the age group of 18-45 years were enrolled in the study. mRNA expression of hTERT and Metallothionein (MT1A) and estimation of telomere length (TL) was done by qPCR and compared. Result: Comparison of groups based on quartiles of TL (groups A-D) revealed an increased expression of hTERT in groups with shorter TL. Expression of MT1A was similar in these groups. Comparison of groups based on quartiles of ∆Ct of MT1A (Groups 1-4) revealed lower TLin groups with low expression of MT1A. Correlation analysis revealed a significant negative correlation between mRNA expression of hTERT with TL (r = - 0.84, p =0.04) and a positive non-significant association between mRNAexpression of MT1Aand TL(r = 0.76, p = 0.2). Conclusion: Our study has documented an increase in expression of hTERT in groups with shorter TL in healthy individuals, reinforcing the role of hTERT in maintenance of telomeres. Caution needs to be maintained when comparing TL/hTERT expression in normal versus diseased individuals. Though our study has documented a possible link between MT1A and TL, the exact role of MT1A with regard to telomere biology needs to be elucidated further.

Keywords

• Healthy individuals, hTERT, MT1A, Telomere length