A polymorphism of the YTHDF2 gene (1p35) located in an Alu-rich genomic domain is associated with human longevity.
The uneven distribution of Alu repetitive elements in the human genome is related to specific functional properties of genomic regions. We report the identification of a locus associated with human longevity in one of the chromosomal regions with the highest density of Alu elements, in 1p35. The locus, corresponding to a (TG)n microsatellite in the YTHDF2 gene, was identified by characterizing an "anonymous" marker detectable through inter-Alu fingerprinting, which previously evidenced an increased homozygosity in centenarians. After genotyping 412 participants of different ages, including 137 centenarians, we confirmed the increased homozygosity in centenarians at this locus, and observed a concomitantly increased frequency of the most frequent allele and the corresponding homozygous genotype. Remarkably, the same genotype was associated with increased YTHDF2 messenger RNA levels in immortalized lymphocytes. Finally, YTHDF2 messenger RNA resulted to be mainly expressed in testis and placenta. The data suggest a possible role of this locus in human longevity.
Cardelli
Maurizio
M
Department of Gerontological Research, Italian National Research Center on Aging (I.N.R.C.A), Via Birarelli 8, 60100 Ancona, Italy. maucard@libero.it
Marchegiani
Francesca
F
Cavallone
Luca
L
Olivieri
Fabiola
F
Giovagnetti
Simona
S
Mugianesi
Elena
E
Moresi
Raffaella
R
Lisa
Rosamaria
R
Franceschi
Claudio
C
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D020087:Alu Elements / Q000235:genetics*; D005260:Female; D005838:Genotype; D006801:Humans; D007438:Introns; D008136:Longevity / Q000235:genetics*; D008214:Lymphocytes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012333:RNA, Messenger / Q000235:genetics*; D020133:Reverse Transcriptase Polymerase Chain Reaction
D012333:RNA, Messenger