title: PTK2 rs7460 and rs7843014 polymorphisms and exceptional longevity: a functional replication study.
abstract: Focal adhesion is critical for cell survival. The focal adhesion kinase (FAK, or PTK2) is an important component of the human interactome and thus is a potential longevity-related protein. Here we studied the association between two PTK2 gene single-nucleotide polymorphisms (SNPs) (rs7843014, rs7460) and exceptional longevity (EL). In addition to gaining insight into their functionality by determining luciferase gene reporter activity, we studied the genotype/allele frequency of these two SNPs among three different cohorts: (1) Spanish centenarians (n=175, 100-111 years, 144 women) and healthy controls (n=355, 20-50 years, 284 women); (2) Italian centenarians (n=79, 100-104 years, 40 women) and controls (n=316, 29-50 years, 156 women); and (3) Japanese centenarians (n=742, 100-116 years, 623 women) and healthy controls (n=499, 23-59 years, 356 women). Both SNPs had functional significance, with the A allele up-regulating luciferase activity compared to the other allele (rs7460 T allele and rs7843014 C allele, respectively). The A allele of both SNPs was negatively associated with EL in the Spanish cohort (rs7460, odds ratio [OR] adjusted by sex=0.40, 95% confidence intervals [CI] 0.3, 0.6, p<0.001); rs7843014, OR=0.37, 95% CI 0.3, 0.5, p<0.001). The OR of being a centenarian if having the rs7460-TT genotype was 6.68 (95% CI 4.1, 10.8, p<0.001). The rs7843014 CC genotype was also positively associated with EL (OR=7.58, 95% CI 4.6, 12.3, p<0.001]. No association was, however, found for the Italian or Japanese cohorts. Thus, two genotypes of the FAK gene, rs7460 TT and rs7843014 CC, are possibly associated with lower gene expression and might favor the likelihood of reaching EL in the Spanish population. Further research is needed to unveil the mechanisms by which FAK expression could perhaps influence the rate of aging.
authors.affiliation: 1 Faculty of Health and Sport Science, University of Zaragoza , Huesca, Spain .
authors.forename: Nuria
authors.initials: N
authors.lastname: Garatachea
authors.forename: Noriyuki
authors.initials: N
authors.lastname: Fuku
authors.forename: Zi-Hong
authors.initials: ZH
authors.lastname: He
authors.forename: Ye
authors.initials: Y
authors.lastname: Tian
authors.forename: Yasumichi
authors.initials: Y
authors.lastname: Arai
authors.forename: Yukiko
authors.initials: Y
authors.lastname: Abe
authors.forename: Haruka
authors.initials: H
authors.lastname: Murakami
authors.forename: Motohiko
authors.initials: M
authors.lastname: Miyachi
authors.forename: Thomas
authors.initials: T
authors.lastname: Yvert
authors.forename: Letizia
authors.initials: L
authors.lastname: Venturini
authors.forename: Catalina
authors.initials: C
authors.lastname: Santiago
authors.forename: Alejandro
authors.initials: A
authors.lastname: Santos-Lozano
authors.forename: Gabriel
authors.initials: G
authors.lastname: Rodríguez
authors.forename: Giovanni
authors.initials: G
authors.lastname: Ricevuti
authors.forename: Helios
authors.initials: H
authors.lastname: Pareja-Galeano
authors.forename: Fabian
authors.initials: F
authors.lastname: Sanchis-Gomar
authors.forename: Enzo
authors.initials: E
authors.lastname: Emanuele
authors.forename: Nobuyoshi
authors.initials: N
authors.lastname: Hirose
authors.forename: Alejandro
authors.initials: A
authors.lastname: Lucia
mesh_terms: D000328:Adult; D000369:Aged, 80 and over; D015331:Cohort Studies; D005260:Female; D051417:Focal Adhesion Kinase 1 / Q000235:genetics*; D005787:Gene Frequency / Q000235:genetics; D056726:Genetic Association Studies; D006801:Humans; D007558:Italy; D007564:Japan; D016015:Logistic Models; D008136:Longevity / Q000235:genetics*; D008156:Luciferases / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide / Q000235:genetics*; D015203:Reproducibility of Results; D013030:Spain; D055815:Young Adult
chemical_list: D008156:Luciferases; D051417:Focal Adhesion Kinase 1; C496050:PTK2 protein, human