Progress 12/01/04 to 11/30/08
Outputs
OUTPUTS: We have identified a U-shaped association between plasma folate status and telomere length in our study population, which was comprised of men. Telomere dysfunction, which is manifest as changes in telomere length, is associated with many age-related diseases including cancer, cardiovascular disease, Alzheimer's disease and Parkiinson's disease. Low folate induced telomere dysfunction could be one of the mechanisms by which folate status influences disease risk. There was a trend for longer telomeres in individuals homozygous for the C677T polymorphism of the methylene tetrahydrofolate reductase gene when folate status was below median. For the microarray analysis, we have completed sample collection and a part of the sample analysis. At this point the data has not been analyzed yet. We will report the results once the data analysis is completed. PARTICIPANTS: Nothing significant to report during this reporting period. TARGET AUDIENCES: Nothing significant to report during this reporting period. PROJECT MODIFICATIONS: Nothing significant to report during this reporting period.
Impacts
Based on our results on the association between telomere length and folate status in men, we are analyzing a larger population (Framingham Heart Study Offspring Cohort [FOS]) to determine this association in both men and women. A larger cohort like FOS can also provide critical data on the association of telomere length with genetic polymorphisms. At this point majority of the data has not been analyzed yet. We will report the results and the impact once the data analysis is completed.
Publications
- Ligi Paul, Marco Cattaneo, Armando D'Angelo, Francesca Sampietro, Isabella Fermo, Cristina Razzari, Gessica Fontana, Nindra Eugene, Paul F. Jacques, Jacob Selhub. Telomere length in peripheral blood mononuclear cells is associated with folate status in men (accepted for publication in Journal of Nutrition 2009)
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Progress 12/01/06 to 11/30/07
Outputs
The protocol for this study is to determine effect of 84 days of supplementation with folic acid or placebo, on DNA methylation and gene expression in individuals homozygous for the CC genotype and TT genotype of the C677T polymorphism of the MTHFR gene. We selected Milan, Italy as the site where the subjects will be recruited from because of the high prevalence of low folate status and homozygotes for this polymorphism. 20 subjects each from the CC genotype and TT genotype have been selected. From each genotype, 10 subjects are given folic acid and 10 subjects are given placebo. Thus far all 40 subjects have been recruited through 2 hospitals in Milan, San Paolo and San Raffaele by our collaborators. The intervention study is at various stages: 13 subjects have completed the study, 23 subjects are within a month or two from completing the study, and 4 subjects will enter the study in January 2008 and will be completing the study by the end of March -beginning of April
2008. By the end of April, my colleague will be traveling to Milan to help prepare the cDNA from the collected blood samples. Microarray experiments will be done at Tufts.
Impacts
Data from the research project have not been generated as of yet. Results of this study will be available by October-November 2008.
Publications
- No publications reported this period
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Progress 12/01/05 to 11/30/07
Outputs
The protocol for this study is to determine effect of 84 days of supplementation with folic acid or placebo, on DNA methylation and gene expression in individuals homozygous for the CC genotype and TT genotype of the C677T polymorphism of the MTHFR gene. We selected Milan, Italy as the site where the subjects will be recruited from because of the high prevalence of low folate status and homozygotes for this polymorphism. 20 subjects each from the CC genotype and TT genotype have been selected. From each genotype, 10 subjects are given folic acid and 10 subjects are given placebo. Thus far all 40 subjects have been recruited through 2 hospitals in Milan, San Paolo and San Raffaele by our collaborators. The intervention study is at various stages: 13 subjects have completed the study, 23 subjects are within a month or two from completing the study, and 4 subjects will enter the study in January 2008 and will be completing the study by the end of March -beginning of
April 2008. By the end of April, my colleague will be traveling to Milan to help prepare the cDNA from the collected blood samples. Microarray experiments will be done at Tufts.
Impacts
Data from the research project have not been generated as of yet. Results of this study will be available by October-November 2008.
Publications
- No publications reported this period
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Progress 12/01/05 to 11/30/06
Outputs
The protocol for this study is to determine effect of 84 days of supplementation with folic acid or placebo, on DNA methylation and gene expression in individuals homozygous for the CC genotype and TT genotype of the C677T polymorphism of the MTHFR gene. We selected Milan, Italy as the site where the subjects will be recruited from because of the high prevalence of low folate status and homozygotes for this polymorphism. 20 subjects each from the CC genotype and TT genotype have been selected. From each genotype, 10 subjects are given folic acid and 10 subjects are given placebo. Thus far all 40 subjects have been recruited through 2 hospitals in Milan, San Paolo and San Raffaele by our collaborators. The intervention study is at various stages: 13 subjects have completed the study, 23 subjects are within a month or two from completing the study, and 4 subjects will enter the study in January 2008 and will be completing the study by the end of March -beginning of
April 2008. By the end of April, my colleague will be traveling to Milan to help prepare the cDNA from the collected blood samples. Microarray experiments will be done at Tufts.
Impacts
Data from the research project have not been generated as of yet. Results of this study will be available by October-November 2008.
Publications
- No publications reported this period
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Progress 12/01/04 to 12/01/05
Outputs
This is a human study project with a great deal complexity, because many of the important features of this projuect are carried out in two institutions in Milan Italy, the UnThis is a human study project with a great deal complexity, because many of the important features of this project are carried out in two institutions in Milan Italy, the University of Milano and Ospidale di San Raffaele. Approval by the respective Institute review boards (IRB) were complex. First the two collaborators, Dr Armando D'Angelo and Dr Marco Cattaneo had to pass the NIH examination for human studies. The study protocol was translated into Italian and back translated into English and all three institutions have finally approved all protocols. We are now awaiting the signing of the contracts by the budget officers of the two respective institutions. We plan to begin the study and start with the screening around February 2006iversity of Milano and Ospidale di San Raffaele. Approval by the
respective Institue review boards (IRB) were complex. First the two collaborators, Dr Armando D'Angelo and Dr Marco Cattaneo had to pass the NIH examination for human studies. The study protocol was translated into Italian and back translated into English and all three institutions have finally approved all protocols. We are now awaiting the signing of the contracts by the budget officers of the two respective institutions. We plan to begin the study and start with the screening around February 2006
Impacts
One of the most important aspects of this study is that the great majority of the studies on epigenetic regulations were done in cell cultures or in animal models. This study will determine the extent to which some of these regulations, e.g. methylation in promoter regions of the genes, can be seen in healthy human volunteers by dietary modifications
Publications
- No publications reported this period
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