Genetic analysis of Paraoxonase (PON1) locus reveals an increased frequency of Arg192 allele in centenarians.
Human Paraoxonase (PON1) is a High-Density Lipoprotein (HDL)-associated esterase that hydrolyses lipo-peroxides. PON1 has recently attracted attention as a protective factor against oxidative modification of LDL and may therefore play an important role in the prevention of the atherosclerotic process. Two polymorphisms have been extensively studied: a Leucine (L allele) to Methionine (M allele) substitution at codon 55, and a Glutamine (A allele) to Arginine (B allele) substitution at codon 192. We have examined these two aminoacidic changes in 579 people aged 20 to 65 years old, and 308 centenarians. We found that the percentage of carriers of the B allele at codon 192 (B+ individuals) is higher in centenarians than in controls (0.539 vs 0.447), moreover we found that among the B+ individuals, the phenomenon was due to an increase of people carrying M alleles at codon 55 locus. In conclusion, we propose that genetic variability at PON1 locus affects survival at extreme advanced age.
Bonafè
Massimiliano
M
Department of Experimental Pathology, Bologna University, Bologna, Italy.
Marchegiani
Francesca
F
Cardelli
Maurizio
M
Olivieri
Fabiola
F
Cavallone
Luca
L
Giovagnetti
Simona
S
Pieri
Carlo
C
Marra
Maurizio
M
Antonicelli
Roberto
R
Troiano
Leonarda
L
Gueresi
Paola
P
Passeri
Giovanni
G
Berardelli
Maurizio
M
Paolisso
Giuseppe
G
Barbieri
Michelangela
M
Tesei
Silvia
S
Lisa
Rosmarie
R
De Benedictis
Giovanna
G
Franceschi
Claudio
C
D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D000375:Aging / Q000235:genetics*; D000483:Alleles; D019943:Amino Acid Substitution; D001120:Arginine; D043303:Aryldialkylphosphatase; D004950:Esterases / Q000235:genetics*; D005260:Female; D005787:Gene Frequency; D006801:Humans; D008136:Longevity / Q000235:genetics*; D008297:Male
D001120:Arginine; D004950:Esterases; D043303:Aryldialkylphosphatase; C468406:PON1 protein, human