The relationship between leukocyte telomere length and TERT, TRF1 single nucleotide polymorphisms in healthy people of different age groups

Biogerontology. 2020 Feb;21(1):57-67. doi: 10.1007/s10522-019-09843-0. Epub 2019 Oct 23.

Abstract

Telomeres are nucleoprotein structures that cap the end of each chromosome and function to maintain genome stability. The length of telomeres is known to shorten with each cell division and it is well-established that telomere attrition is related to replicative capacity in vitro. Moreover, telomere loss is also correlated with the process of aging in vivo. That is why we aimed to find any associations of leukocyte telomere shortening with different age groups. We enrolled 291 healthy people in a study group. Samples of DNA from peripheral blood leukocytes were purified by the DNA salting-out method. The genotyping was carried out using the real-time polymerase chain reaction. The results were assessed using the statistical analysis software ''IBM SPSS Statistics 23.0". To determine the relationship between the leukocyte telomere length and single nucleotide polymorphisms of TERT and TRF1 and the age of healthy individuals. The relative leukocyte telomere length (T/S) measurement was performed in study subjects and compared between different age groups. We found that T/S in the first age group was statistically significantly higher than in the second group (p = 0.040), while in the second and the third age groups T/S was statistically significantly lower than in the fourth age group (p < 0.001 and p = 0.001 respectively). There was also a weak negative but statistically significant inverse correlation between the age of the subjects and the length of telomeres (p = 0.025). We found that TRF1 rs10107605 CC genotype was statistically significantly more frequent in subjects with long telomeres than in subjects with short telomeres (p = 0.009). The TRF1 rs10107605 CC genotype compared to AA genotype was associated with 75% decreased odds of telomere shortening (p = 0.017), and the CC genotype compared to AA + AC genotypes was associated with 75% decreased odds (p = 0.014). T/S correlates with age negatively. The frequencies of genotypes and alleles of TERT rs2736098, rs401681 and TRF1 rs1545827 did not differ between different age groups. The TRF1 rs10107605 polymorphism is associated with telomere shortening.

Keywords: TERT; TRF1; Telomerase; Telomere; Telomere length; rs10107605; rs1545827; rs2736098; rs401681.

MeSH terms

  • Adult
  • Age Factors
  • Aged
  • Aged, 80 and over
  • DNA Replication
  • Female
  • Genotype
  • Humans
  • Leukocytes / cytology
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Telomerase / genetics*
  • Telomere / genetics*
  • Telomere Shortening
  • Telomeric Repeat Binding Protein 1 / genetics*
  • Young Adult

Substances

  • Telomeric Repeat Binding Protein 1
  • TERT protein, human
  • Telomerase