Anti-Inflammatory Heat Shock Protein 70 Genes are Positively Associated with Human Survival

Ripudaman Singh, Steen Kølvraa, Peter Gerd Bross, Kaare Christensen, Lise Bathum, Niels Gregersen, Qihua Tan, Suresh Rattan

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

Resumé

A positive relationship between stress tolerance and longevity has been observed in several model systems. That the same correlation is applicable in humans and that it may be open to experimental manipulation for extending human lifespan requires studies on association of stress genes with longevity. The involvement of heat shock protein 70 (Hsp70) in cellular maintenance and repair mechanisms, including its role as an anti-inflammatory protein, makes it a suitable candidate for studying such associations. We have studied the association of three single nucleotide polymorphisms, HSPA1A (-110A>C), HSPA1B (1267A>G), and HSPA1L (2437T>C), present in the three HSP70 genes, with human survival, in a cohort of individuals born in the year 1905. This population cohort is a part of the longitudinal study of Danish nonagenarians. Since DNA samples were already collected in 1998, this gave us the opportunity to perform survival analysis on these subjects. Haplotype relative risk, and genotype relative risk were calculated to measure the effects of haplotypes and genotypes on human survival in a sex-specific manner. A significant association of HSPA1A-AA (RR=3.864; p=0.016) and HSPA1B-AA (RR=2.764; p=0.039) genotypes with poor survival was observed in female subjects. Also the female carriers of haplotype G-C-T had longer survival than the non-carriers (HRR=0.550; p=0.015). On an average, female carriers of the G-C-T haplotype live about one year longer than non-carriers. This result corroborates our previous observations from heat shock response (HSR) study where we had shown that after heat stimulation, mononuclear cells from the carriers of genotype HSPA1L-TT had better HSR than cells with the HSPA1L-CC genotype.

OriginalsprogEngelsk
TidsskriftCurrent Pharmaceutical Design
Vol/bind16
Udgave nummer7
Sider (fra-til)796-801
Antal sider6
ISSN1381-6128
DOI
StatusUdgivet - 2010

Fingeraftryk

HSP70 Heat-Shock Proteins
Haplotypes
Heat-Shock Response
Survival Analysis
Single Nucleotide Polymorphism
Longitudinal Studies
Maintenance
DNA
Population
Proteins

Emneord

  • Aldring
  • Aldringsstudier

Citer dette

Singh, Ripudaman ; Kølvraa, Steen ; Bross, Peter Gerd ; Christensen, Kaare ; Bathum, Lise ; Gregersen, Niels ; Tan, Qihua ; Rattan, Suresh. / Anti-Inflammatory Heat Shock Protein 70 Genes are Positively Associated with Human Survival. I: Current Pharmaceutical Design. 2010 ; Bind 16, Nr. 7. s. 796-801.
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abstract = "A positive relationship between stress tolerance and longevity has been observed in several model systems. That the same correlation is applicable in humans and that it may be open to experimental manipulation for extending human lifespan requires studies on association of stress genes with longevity. The involvement of heat shock protein 70 (Hsp70) in cellular maintenance and repair mechanisms, including its role as an anti-inflammatory protein, makes it a suitable candidate for studying such associations. We have studied the association of three single nucleotide polymorphisms, HSPA1A (-110A>C), HSPA1B (1267A>G), and HSPA1L (2437T>C), present in the three HSP70 genes, with human survival, in a cohort of individuals born in the year 1905. This population cohort is a part of the longitudinal study of Danish nonagenarians. Since DNA samples were already collected in 1998, this gave us the opportunity to perform survival analysis on these subjects. Haplotype relative risk, and genotype relative risk were calculated to measure the effects of haplotypes and genotypes on human survival in a sex-specific manner. A significant association of HSPA1A-AA (RR=3.864; p=0.016) and HSPA1B-AA (RR=2.764; p=0.039) genotypes with poor survival was observed in female subjects. Also the female carriers of haplotype G-C-T had longer survival than the non-carriers (HRR=0.550; p=0.015). On an average, female carriers of the G-C-T haplotype live about one year longer than non-carriers. This result corroborates our previous observations from heat shock response (HSR) study where we had shown that after heat stimulation, mononuclear cells from the carriers of genotype HSPA1L-TT had better HSR than cells with the HSPA1L-CC genotype.",
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Anti-Inflammatory Heat Shock Protein 70 Genes are Positively Associated with Human Survival. / Singh, Ripudaman; Kølvraa, Steen; Bross, Peter Gerd; Christensen, Kaare; Bathum, Lise; Gregersen, Niels; Tan, Qihua; Rattan, Suresh.

I: Current Pharmaceutical Design, Bind 16, Nr. 7, 2010, s. 796-801.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningpeer review

TY - JOUR

T1 - Anti-Inflammatory Heat Shock Protein 70 Genes are Positively Associated with Human Survival

AU - Singh, Ripudaman

AU - Kølvraa, Steen

AU - Bross, Peter Gerd

AU - Christensen, Kaare

AU - Bathum, Lise

AU - Gregersen, Niels

AU - Tan, Qihua

AU - Rattan, Suresh

PY - 2010

Y1 - 2010

N2 - A positive relationship between stress tolerance and longevity has been observed in several model systems. That the same correlation is applicable in humans and that it may be open to experimental manipulation for extending human lifespan requires studies on association of stress genes with longevity. The involvement of heat shock protein 70 (Hsp70) in cellular maintenance and repair mechanisms, including its role as an anti-inflammatory protein, makes it a suitable candidate for studying such associations. We have studied the association of three single nucleotide polymorphisms, HSPA1A (-110A>C), HSPA1B (1267A>G), and HSPA1L (2437T>C), present in the three HSP70 genes, with human survival, in a cohort of individuals born in the year 1905. This population cohort is a part of the longitudinal study of Danish nonagenarians. Since DNA samples were already collected in 1998, this gave us the opportunity to perform survival analysis on these subjects. Haplotype relative risk, and genotype relative risk were calculated to measure the effects of haplotypes and genotypes on human survival in a sex-specific manner. A significant association of HSPA1A-AA (RR=3.864; p=0.016) and HSPA1B-AA (RR=2.764; p=0.039) genotypes with poor survival was observed in female subjects. Also the female carriers of haplotype G-C-T had longer survival than the non-carriers (HRR=0.550; p=0.015). On an average, female carriers of the G-C-T haplotype live about one year longer than non-carriers. This result corroborates our previous observations from heat shock response (HSR) study where we had shown that after heat stimulation, mononuclear cells from the carriers of genotype HSPA1L-TT had better HSR than cells with the HSPA1L-CC genotype.

AB - A positive relationship between stress tolerance and longevity has been observed in several model systems. That the same correlation is applicable in humans and that it may be open to experimental manipulation for extending human lifespan requires studies on association of stress genes with longevity. The involvement of heat shock protein 70 (Hsp70) in cellular maintenance and repair mechanisms, including its role as an anti-inflammatory protein, makes it a suitable candidate for studying such associations. We have studied the association of three single nucleotide polymorphisms, HSPA1A (-110A>C), HSPA1B (1267A>G), and HSPA1L (2437T>C), present in the three HSP70 genes, with human survival, in a cohort of individuals born in the year 1905. This population cohort is a part of the longitudinal study of Danish nonagenarians. Since DNA samples were already collected in 1998, this gave us the opportunity to perform survival analysis on these subjects. Haplotype relative risk, and genotype relative risk were calculated to measure the effects of haplotypes and genotypes on human survival in a sex-specific manner. A significant association of HSPA1A-AA (RR=3.864; p=0.016) and HSPA1B-AA (RR=2.764; p=0.039) genotypes with poor survival was observed in female subjects. Also the female carriers of haplotype G-C-T had longer survival than the non-carriers (HRR=0.550; p=0.015). On an average, female carriers of the G-C-T haplotype live about one year longer than non-carriers. This result corroborates our previous observations from heat shock response (HSR) study where we had shown that after heat stimulation, mononuclear cells from the carriers of genotype HSPA1L-TT had better HSR than cells with the HSPA1L-CC genotype.

KW - Aldring

KW - Aldringsstudier

KW - HSP70 Heat-Shock Proteins

KW - HSR

KW - HSP70

KW - Aging

KW - Longevity

KW - Survival

KW - Haplotype

KW - Polymorphisms

U2 - 10.2174/138161210790883499

DO - 10.2174/138161210790883499

M3 - Journal article

VL - 16

SP - 796

EP - 801

JO - Current Pharmaceutical Design

JF - Current Pharmaceutical Design

SN - 1381-6128

IS - 7

ER -