HSPA1B
Heat shock 70 kDa protein 1B (Heat shock 70 kDa protein 2) (HSP70-2) (HSP70.2) [HSP72]
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Mounting evidence suggests that all organisms at the cellular level respond to stress by synthesizing heat shock proteins at the expense of other proteins, and the ability of human cells to respond to heat stress decreases with aging. We thus investigate the association of 3 variants (A1267G in HSPA1B, G190C in HSPA1A, and T2437C in HSPA1L) in the heat shock protein 70 (Hsp70) family with natural longevity in a Xinjiang Hetian Uygur population. A case-control study was conducted in 191 healthy individuals greater than 90 years of age, and 53 naturally died persons 65-70 years of age. Promoter activity was evaluated by luciferase reporter assays. The data were analyzed using an EH/EH program for haplotype prediction and MDR software for gene-gene interaction. All studied variants satisfied the Hardy-Weinberg equilibrium in each group. In single-locus analysis, no significant differences were found between long-lived people and short-lived people in the genotype/allele distributions of all variants. In contrast, haplotype analysis indicated that haplotypes A-G-C and A-C-T were more prevalent in long-lived people than short-lived people (P=0.026 and 0.017), and the analysis conferred a 3.46- and 4.51-fold increased tendency for longevity, respectively (P=0.025 and 0.016). The haplotype results were strengthened by interaction analysis, which suggests an optimal model in which G190C and T2437C exert an interacting effect on longevity. No functional significance was observed between 190G and 190C alleles in both control and heat-inducible A549 cells (P>0.05). Taken together, our findings suggested that common genetic variants in Hsp70 family might contribute interactively to longevity the Xinjiang Hetian Uygur population.
MeSH Terms
- Aged
- Aged, 80 and over
- Asian Continental Ancestry Group
- Case-Control Studies
- China
- DNA Mutational Analysis
- Ethnic Groups
- Female
- Genotype
- HSP70 Heat-Shock Proteins
- Humans
- Longevity
- Male
- Phenotype
- Polymorphism, Genetic
Human longevity is determined to a certain extent by genetic factors. Several candidate genes have been studied for their association with human longevity, but the data collected so far are inconclusive. One of the reasons is the choice of the candidate genes in addition to the choice of an appropriate study design and methodology. Since aging is characterized by a progressive accumulation of molecular damage and an attenuation of the cellular defense mechanisms, the focus of studies on human longevity association with genes has now shifted to the pathways of cellular maintenance and repair mechanisms. One such pathway includes the battery of stress response genes, especially the heat shock protein HSP70 genes. Three such genes, HSPA1A, HSPA1B and HSPA1L, are present within the MHC-III region on the short arm of chromosome 6. We and others have found alleles, genotypes and haplotypes which have been significantly associated with human longevity and survival. We have also provided some functional evidence for these genetic associations by showing that isolated peripheral blood cells from those genotypes which are negatively associated with human longevity also have less ability to respond to heat shock. Stress response genes, particularly HSP70, are now the major candidates in the gene-longevity association studies.
MeSH Terms
- Aging
- HSP70 Heat-Shock Proteins
- Humans
- Longevity