title: The functional VNTR MNS16A of the TERT gene is associated with human longevity in a population of Central Italy.
abstract: BACKGROUND
  Telomerase, encoded by TERT, is the ribonucleoprotein polymerase that maintains telomere ends and it plays a crucial role in cellular senescence. TERT single nucleotide polymorphisms (SNPs) have been associated both with various malignancies and telomere length (TL). The association of TERT SNPs with longevity remains uncertain and varies with ethnicity. The aim of this study was to investigate whether the functional variable number of tandem repeat (VNTR) MNS16A of TERT is associated with longevity.
  
  
  METHODS
  MNS16A genotypes have been determined for 1072 unrelated healthy individuals from Central Italy (18-106 years old) divided into three gender-specific age classes defined according to demographic information and accounting for the different survivals between sexes: for men (women), the first class consists of individuals <66 years old (<73 years old), the second class of individuals 66-88 years old (73-91 years old), and the third class of individuals >88 years old (>91 years old). TL was assessed using genomic DNA from whole blood of 72 selected individuals by a multiplex real-time PCR assay.
  
  
  RESULTS
  MNS16A appears associated to longevity, showing significant associations in Comparison 2 (Age Class 3 vs. Age Class 2) under both additive (odds ratio [O.R.] 0.749; p=0.019) and dominant (O.R. 0.579; p=0.011) models. The MNS16A*L allele is significantly underrepresented in Age Class 3 (O.R. 0.759; p=0.020) compared to Age Class 2. A significant telomere attrition is reported along the three age classes (p=0.0001), that remains significant only in L*/L* genotype carriers (p=0.002) when the analysis was conducted according to MNS16A genotype.
  
  
  CONCLUSIONS
  The TERT MNS16A*L allele appears negatively associated with longevity. The concomitant significant telomere cross sectional attrition rate observed for L*/L* genotype suggests that this polymorphism could influence human longevity by affecting TL.
authors.affiliation: School of Biosciences and Biotechnologies, University of Camerino, Camerino, Italy.
authors.forename: Fabio
authors.initials: F
authors.lastname: Concetti
authors.forename: Nazzareno
authors.initials: N
authors.lastname: Lucarini
authors.forename: Francesco M
authors.initials: FM
authors.lastname: Carpi
authors.forename: Fabio
authors.initials: F
authors.lastname: Di Pietro
authors.forename: Serena
authors.initials: S
authors.lastname: Dato
authors.forename: Melania
authors.initials: M
authors.lastname: Capitani
authors.forename: Massimo
authors.initials: M
authors.lastname: Nabissi
authors.forename: Giorgio
authors.initials: G
authors.lastname: Santoni
authors.forename: Fiorenzo
authors.initials: F
authors.lastname: Mignini
authors.forename: Giuseppe
authors.initials: G
authors.lastname: Passarino
authors.forename: Valerio
authors.initials: V
authors.lastname: Napolioni
mesh_terms: D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D005260:Female; D020022:Genetic Predisposition to Disease; D006801:Humans; D007558:Italy; D008136:Longevity / Q000235:genetics*; D008297:Male; D008875:Middle Aged; D018598:Minisatellite Repeats / Q000235:genetics*; D020641:Polymorphism, Single Nucleotide; D012307:Risk Factors; D019098:Telomerase / Q000235:genetics*; D044465:White People / Q000235:genetics; D055815:Young Adult
chemical_list: C509186:TERT protein, human; D019098:Telomerase