PTK2 rs7460 and rs7843014 polymorphisms and exceptional longevity: A functional replication study

Nuria Garatachea, Noriyuki Fuku, Zi Hong He, Ye Tian, Yasumichi Arai, Yukiko Abe, Haruka Murakami, Motohiko Miyachi, Thomas Yvert, Letizia Venturini, Catalina Santiago, Alejandro Santos-Lozano, Gabriel Rodríguez, Giovanni Ricevuti, Helios Pareja-Galeano, Fabian Sanchis-Gomar, Enzo Emanuele, Nobuyoshi Hirose, Alejandro Lucia

研究成果: Article

5 引用 (Scopus)

抄録

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.

元の言語English
ページ(範囲)430-438
ページ数9
ジャーナルRejuvenation Research
17
発行部数5
DOI
出版物ステータスPublished - 2014 10 1

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Alleles
Single Nucleotide Polymorphism
Odds Ratio
Genotype
Confidence Intervals
Luciferases
Focal Adhesion Protein-Tyrosine Kinases
Focal Adhesions
Reporter Genes
Gene Frequency
Genes
Cell Survival
Gene Expression
Research
Population
Proteins

ASJC Scopus subject areas

  • Ageing
  • Geriatrics and Gerontology
  • Medicine(all)

これを引用

PTK2 rs7460 and rs7843014 polymorphisms and exceptional longevity : A functional replication study. / Garatachea, Nuria; Fuku, Noriyuki; He, Zi Hong; Tian, Ye; Arai, Yasumichi; Abe, Yukiko; Murakami, Haruka; Miyachi, Motohiko; Yvert, Thomas; Venturini, Letizia; Santiago, Catalina; Santos-Lozano, Alejandro; Rodríguez, Gabriel; Ricevuti, Giovanni; Pareja-Galeano, Helios; Sanchis-Gomar, Fabian; Emanuele, Enzo; Hirose, Nobuyoshi; Lucia, Alejandro.

:: Rejuvenation Research, 巻 17, 番号 5, 01.10.2014, p. 430-438.

研究成果: Article

Garatachea, N, Fuku, N, He, ZH, Tian, Y, Arai, Y, Abe, Y, Murakami, H, Miyachi, M, Yvert, T, Venturini, L, Santiago, C, Santos-Lozano, A, Rodríguez, G, Ricevuti, G, Pareja-Galeano, H, Sanchis-Gomar, F, Emanuele, E, Hirose, N & Lucia, A 2014, 'PTK2 rs7460 and rs7843014 polymorphisms and exceptional longevity: A functional replication study', Rejuvenation Research, 巻. 17, 番号 5, pp. 430-438. https://doi.org/10.1089/rej.2014.1570
Garatachea, Nuria ; Fuku, Noriyuki ; He, Zi Hong ; Tian, Ye ; Arai, Yasumichi ; Abe, Yukiko ; Murakami, Haruka ; Miyachi, Motohiko ; Yvert, Thomas ; Venturini, Letizia ; Santiago, Catalina ; Santos-Lozano, Alejandro ; Rodríguez, Gabriel ; Ricevuti, Giovanni ; Pareja-Galeano, Helios ; Sanchis-Gomar, Fabian ; Emanuele, Enzo ; Hirose, Nobuyoshi ; Lucia, Alejandro. / PTK2 rs7460 and rs7843014 polymorphisms and exceptional longevity : A functional replication study. :: Rejuvenation Research. 2014 ; 巻 17, 番号 5. pp. 430-438.
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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.",
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T1 - PTK2 rs7460 and rs7843014 polymorphisms and exceptional longevity

T2 - A functional replication study

AU - Garatachea, Nuria

AU - Fuku, Noriyuki

AU - He, Zi Hong

AU - Tian, Ye

AU - Arai, Yasumichi

AU - Abe, Yukiko

AU - Murakami, Haruka

AU - Miyachi, Motohiko

AU - Yvert, Thomas

AU - Venturini, Letizia

AU - Santiago, Catalina

AU - Santos-Lozano, Alejandro

AU - Rodríguez, Gabriel

AU - Ricevuti, Giovanni

AU - Pareja-Galeano, Helios

AU - Sanchis-Gomar, Fabian

AU - Emanuele, Enzo

AU - Hirose, Nobuyoshi

AU - Lucia, Alejandro

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Y1 - 2014/10/1

N2 - 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.

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