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Peer-reviewedCC BY 4.0International Journal of Molecular Sciences

Telomere-Independent Associations of hTERT Promoter Polymorphisms with Metabolic Phenotypes and Diabetic Complications

  • Krzysztof Sawicki1
  • Małgorzata Suchecka2
  • Magdalena Matysiak-Kucharek1
  • Marcin Kruszewski1,3
  • Paulina Wojtyła-Buciora4
  • Piotr Dziemidok2
  • Lucyna Kapka-Skrzypczak1,5
5 affiliations
  1. 1Department of Molecular Biology and Translational Research, Institute of Rural Health, 20-090 Lublin, Poland
  2. 2Department of Diabetes, Institute of Rural Health, 20-090 Lublin, Poland
  3. 3Centre for Radiobiology and Biological Dosimetry, Institute of Nuclear Chemistry and Technology, 03-195 Warsaw, Poland
  4. 4Faculty of Medicine and Health Promotion, University of Kalisz, 62-800 Kalisz, Poland
  5. 5World Institute for Family Health, University of Kalisz, 62-800 Kalisz, Poland
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Abstract

This study investigated association of three hTERT promoter polymorphisms (rs2735940, rs7712562, rs2853669) with leukocyte relative telomere length (RTL) and clinical characteristics, in patients with type 1 (T1DM) and type 2 (T2DM) diabetes. Covariate-adjusted ANCOVA revealed no significant direct association between hTERT variants and leukocyte RTL in either cohort. However, nominally significant, RTL-independent clinical associations emerged in T2DM patients. Multivariate logistic regression associated the rs2853669 CC genotype with lower odds of diabetic neuropathy (OR = 0.324, 95% CI: 0.106–0.989, raw p = 0.048). Furthermore, the rs2735940 TT genotype was associated with a favorable lipid profile (lower TC, LDL, and non-HDL; raw p < 0.05), while rs7712562 CC carriers exhibited higher waist circumference (raw p = 0.016). While hTERT variants were not directly associated with RTL under severe metabolic stress, they exhibited clinically relevant phenotypic associations. Although these exploratory secondary findings did not survive False Discovery Rate (FDR) correction, the nominal association of rs2853669 CC with lower neuropathy odds suggests potential non-telomeric pathways associated with mitochondrial protection. These hypothesis-generating observations warrant independent validation in larger, prospective cohorts.

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Cite

BibTeXRIS
BibTeX
@article{sawicki2026telomereindependent,
  title = {{Telomere-Independent Associations of hTERT Promoter Polymorphisms with Metabolic Phenotypes and Diabetic Complications}},
  author = {Krzysztof Sawicki and Małgorzata Suchecka and Magdalena Matysiak-Kucharek and Marcin Kruszewski and Paulina Wojtyła-Buciora and Piotr Dziemidok and Lucyna Kapka-Skrzypczak},
  journal = {International Journal of Molecular Sciences},
  year = {2026},
  month = oct,
  doi = {10.3390/ijms27209292},
  url = {https://www.mdpi.com/1422-0067/27/20/9292},
  note = {CC BY 4.0},
}
RIS
TY  - JOUR
TI  - Telomere-Independent Associations of hTERT Promoter Polymorphisms with Metabolic Phenotypes and Diabetic Complications
AU  - Krzysztof Sawicki
AU  - Małgorzata Suchecka
AU  - Magdalena Matysiak-Kucharek
AU  - Marcin Kruszewski
AU  - Paulina Wojtyła-Buciora
AU  - Piotr Dziemidok
AU  - Lucyna Kapka-Skrzypczak
PY  - 2026
DA  - 2026/10/01
JO  - International Journal of Molecular Sciences
DO  - 10.3390/ijms27209292
UR  - https://www.mdpi.com/1422-0067/27/20/9292
AB  - This study investigated association of three hTERT promoter polymorphisms (rs2735940, rs7712562, rs2853669) with leukocyte relative telomere length (RTL) and clinical characteristics, in patients with type 1 (T1DM) and type 2 (T2DM) diabetes. Covariate-adjusted ANCOVA revealed no significant direct association between hTERT variants and leukocyte RTL in either cohort. However, nominally significant, RTL-independent clinical associations emerged in T2DM patients. Multivariate logistic regression associated the rs2853669 CC genotype with lower odds of diabetic neuropathy (OR = 0.324, 95% CI: 0.106–0.989, raw p = 0.048). Furthermore, the rs2735940 TT genotype was associated with a favorable lipid profile (lower TC, LDL, and non-HDL; raw p < 0.05), while rs7712562 CC carriers exhibited higher waist circumference (raw p = 0.016). While hTERT variants were not directly associated with RTL under severe metabolic stress, they exhibited clinically relevant phenotypic associations. Although these exploratory secondary findings did not survive False Discovery Rate (FDR) correction, the nominal association of rs2853669 CC with lower neuropathy odds suggests potential non-telomeric pathways associated with mitochondrial protection. These hypothesis-generating observations warrant independent validation in larger, prospective cohorts.
SN  - 1422-0067
ER  -