Method of Using FOXO3A Polymorphisms and Haplotypes to Predict and Promote Healthy Aging and Longevity

Abstract

The invention provides methods and compositions relating to identification and use of genetic information from the FOXO3A gene that can be used for determining and increasing an individual's likelihood of longevity and of retaining physical and cognitive function during aging, and for determining and decreasing an individual's likelihood of developing a cardiovascular-, metabolic- or age-related disease, including coronary artery (heart) disease, stroke, cancer, chronic pulmonary disease, diabetes, Parkinson's disease and dementia.

1 . A method of diagnosing a predisposition to longevity in a subject, which comprises determining in a tissue sample of said subject whether said subject possesses at least one “G” allele of locus/polymorphism rs2802292 at position 109015211 in the FOXO3A gene on chromosome 6. 
     
     
         2 . The method of  claim 1 , wherein longevity is living at least an additional 15 years and said predisposition further includes a predisposition to freedom from of at least one chronic disease associated with aging. 
     
     
         3 . The method of  claim 2 , wherein at least one chronic disease associated with aging is selected from the group consisting of diabetes, coronary artery disease and cancer. 
     
     
         4 . A method of diagnosing a predisposition to longevity in a subject, which comprises determining in a tissue sample of said subject whether said subject possesses at least one “C” allele of locus/polymorphism rs2764264 at position 109041154 in the FOXO3A gene on chromosome 6. 
     
     
         5 . The method of  claim 1 , wherein longevity is living at least an additional 15 years and said predisposition further includes a predisposition to freedom from of at least one chronic disease associated with aging. 
     
     
         6 . The method of  claim 2 , wherein at least one chronic disease associated with aging is selected from the group consisting of diabetes, coronary artery disease and cancer 
     
     
         7 . A method of diagnosing a predisposition to longevity in a subject, which comprises determining in a tissue sample of said subject whether said subject possesses at least one “C” allele of locus/polymorphism rs13217795 at position 109080791 in the FOXO3A gene on chromosome 6. 
     
     
         8 . The method of  claim 7 , wherein longevity is living at least an additional 15 years and said predisposition further includes a predisposition to freedom from of at least one chronic disease associated with aging. 
     
     
         9 . The method of  claim 8  wherein at least one chronic disease associated with aging is selected from the group consisting of diabetes, coronary artery disease and cancer 
     
     
         10 . The method of  claim 1 , wherein longevity is living at least an additional 15 years and said predisposition further includes a predisposition to freedom from of at least one chronic disease associated with aging. 
     
     
         11 . A method of diagnosing a predisposition to longevity in a subject, which comprises determining in a tissue sample of said subject whether said subject possesses a “GCC” haplotype, the “GCC” haplotype being loci/polymorphisms rs2802292, rs2764264, rs13217795, respectively, in a FOXO3A gene. 
     
     
         12 . A method of diagnosing a predisposition to longevity in a non-human subject, which comprises determining in a tissue sample of said subject whether said subject possesses a non-human homologue to a “GCC” haplotype, said “GCC” haplotype being loci/polymorphisms rs2802292, rs2764264, rs13217795, respectively, in a FOXO3A gene. 
     
     
         13 . A kit comprising a first nucleic acid of sufficient length to hybridizes to a first target nucleic acid sequence position selected from the group consisting of a “G” allele of locus/polymorphism rs2802292 at position 109015211 in the FOXO3A gene on chromosome 6, a “G” allele of locus/polymorphism rs2802292 at position 109015211 in the FOXO3A gene on chromosome 6 and a “C” allele of locus/polymorphism rs2764264 at position 109041154 in the FOXO3A gene on chromosome 6, wherein said first nucleic acid hybridizes to said first target nucleic acid sequence at the position, or the complement of said first target nucleic acid sequence, in one or more containers and instructions for use. 
     
     
         14 . A method for testing for the presence of at least one allele of a FOXO3A haplotype comprising the steps of:
 a) collecting a sample of cells from a subject;   b) isolating a nucleic acid sample from the cells of the sample;   c) contacting the nucleic acid sample with at least one primer which specifically hybridizes 5′ and 3′ to at least one allele of a FOXO3A haplotype under conditions such that hybridization and amplification of the allele occurs; and   d) detecting the amplification product by allele detection means.   
     
     
         15 . The method according to  claim 14 , wherein at least one primer is selected from the group consisting of SEQ ID NOS. 5-8. 
     
     
         16 . A method of monitoring the treatment of a subject with a therapeutic agent by monitoring the level of gene expression of a gene associated with longevity comprising:
 a) obtaining a pre-administration sample from a subject prior to administration of the therapeutic agent;   b) detecting the level of gene expression in the pre-administration sample;   c) obtaining one or more post-administration samples from the subject;   d) detecting the level of gene expression in the post-administration sample;   e) comparing the level of gene expression in the pre- and post-administrative samples to determine the effect of the therapeutic agent on gene expression; and   f) altering the treatment of the subject based on the effect of the therapeutic agent on gene expression.   
     
     
         17 . The method of  claim 16 , wherein the detecting the level of gene expression comprises determining at least one of the protein, mRNA or DNA transcription level of the gene associated with longevity. 
     
     
         18 . The method according to  claim 16 , wherein the gene associated with longevity is selected from the group consisting of FOXO3A, LOC100130966, anon-human homologue of FOXO3A, and a non-human homologue of LOC100130966. 
     
     
         19 . The use of the presence or absence of the “GCC” FOXO3A haplotype in a risk calculator to aid in the prediction of death, age-associated diseases or future physical function.