Genetic polymorphisms affecting telomere length and their association with cardiovascular disease in the Heinz-Nixdorf-Recall study

PLoS One. 2024 May 14;19(5):e0303357. doi: 10.1371/journal.pone.0303357. eCollection 2024.

Abstract

Short telomeres are associated with cardiovascular disease (CVD). We aimed to investigate, if genetically determined telomere-length effects CVD-risk in the Heinz-Nixdorf-Recall study (HNRS) population. We selected 14 single-nucleotide polymorphisms (SNPs) associated with telomere-length (p<10-8) from the literature and after exclusion 9 SNPs were included in the analyses. Additionally, a genetic risk score (GRS) using these 9 SNPs was calculated. Incident CVD was defined as fatal and non-fatal myocardial infarction, stroke, and coronary death. We included 3874 HNRS participants with available genetic data and had no known history of CVD at baseline. Cox proportional-hazards regression was used to test the association between the SNPs/GRS and incident CVD-risk adjusting for common CVD risk-factors. The analyses were further stratified by CVD risk-factors. During follow-up (12.1±4.31 years), 466 participants experienced CVD-events. No association between SNPs/GRS and CVD was observed in the adjusted analyses. However, the GRS, rs10936599, rs2487999 and rs8105767 increase the CVD-risk in current smoker. Few SNPs (rs10936599, rs2487999, and rs7675998) showed an increased CVD-risk, whereas rs10936599, rs677228 and rs4387287 a decreased CVD-risk, in further strata. The results of our study suggest different effects of SNPs/GRS on CVD-risk depending on the CVD risk-factor strata, highlighting the importance of stratified analyses in CVD risk-factors.

MeSH terms

  • Aged
  • Cardiovascular Diseases* / genetics
  • Female
  • Genetic Predisposition to Disease*
  • Humans
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide*
  • Risk Factors
  • Telomere Homeostasis / genetics
  • Telomere* / genetics

Grants and funding

Financial support for the Heinz Nixdorf Recall Study was received from the Heinz Nixdorf Foundation [Chairman: M. Nixdorf; Past Chairman: G. Schmidt‡], the “Deutsche Forschungsgemeinschaft” (Project numbers: SP: PE 2309/2-1, and RE: ER 155/6-1) and the “Bundesministerium für Bildung und Forschung” for the generous support of this study. We thank the Ministry of Innovation, Science and Research, Nordrhine-Westfalia for the generous support for the genotyping of the Heinz Nixdorf Recall study participants. GE Imatron Inc., South San Francisco, CA and Sarstedt AG & Co. (Nümbrecht, Germany) provided financial support for EBCT scanners and laboratory equipment. We acknowledge support by the Open Access Publication Fund of the University of Duisburg-Essen. The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.