Analogous telomeres shortening and different metabolic profile: hypertension versus hypertension/type 2 diabetes mellitus comorbidity

Abstract

Background: Eukaryotes chromosomal ends are capped and protected by telomeres, which are noncoding DNA repeats synthesized by telomerase enzyme. The telomerase enzyme is a nucleoprotein encoded by TERC and TERT genes. Naturally, the length of the telomeres shortens with each cell cycle but the shortening is fastened in certain age-related diseases like hypertension (HTN) and type 2 diabetes mellitus (T2DM).

Materials and methods: Blood samples (n = 171) were obtained from Kuwaiti subjects with HTN, and HTN/T2DM comorbidity (HTN-DM) and healthy subjects. The leukocyte telomere length (LTL) was measured by SYBR green quantitative rtPCR, and plasma telomerase enzyme was measured by ELISA, in addition, three single nucleotide polymorphisms (SNPs) in telomere-related genes; TERC rs12696304GC, TERT rs2736100CA, and ACYP2 rs6713088GC were genotyped by real-time PCR.

Results: Marked LTL shortening in subjects with HTN and HTN-DM compared to healthy subjects, P = 0.043 and P < 0.001, respectively, was noticed. On the contrary, the plasma telomerase enzyme levels and minor allele frequencies and genotypes of the tested SNPs were comparable between the study groups, except for TERT (CA) genotype which was over-represented in HTN (P = 0.037). Furthermore, the comparisons between HTN and HTN-DM revealed significantly higher total cholesterol (P = 0.015) and LDL-C (P = 0.008) in HTN, while higher insulin levels (P < 001), HOMA-IR (P < 001), and BMI (P = 0.004) were observed in HTN-DM.

Conclusion: This study showed comparable LTL shortening in HTN and HTN-DM, irrespective of plasma telomerase enzyme levels or tested TERC, TERT, and ACYP2 gene polymorphisms, although HTN and HTN-DM differed in several metabolic markers. More studies are required to affirm these observations.

Keywords: Kuwait; biochemical profile; hypertension; single nucleotide polymorphism; telomerase; telomeres; type 2 diabetes mellitus.

Fig. 1

(a) The mean leukocyte telomere length (LTL) in patients with hypertension (HTN) and hypertension associated with type 2 diabetes mellitus (HTN-DM) which was significantly shorter than in healthy subjects, but no significant difference between the HTN and HTN-DM groups (P = 0.068). (b) The plasma telomerase enzyme concentration in the three study groups; HTN, healthy control, and HTN-DM. The analysis showed no significant differences between the groups. In (a) and (b), the box bottom and top borders are 25 and 75%, central line is median value and vertical line ends are 5 and 95%, while the closed circles are outliers. (c) Shows correlation of the LTL (kb) in x axis with plasma telomerase enzyme concentration (U/L) in y axis, for all study groups taken together. The closed circles stand for each study subject and the line is the plot regression line, which showed no significant correlation (CC-0.0126, P = 0.894) between the two parameters.