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The role of nutritional and genetic ...

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The role of nutritional and genetic factors of one-carbon transfer pathways in frailty syndrome in older women.

Record Type:	Language materials, printed : Monograph/item
Title/Author:	The role of nutritional and genetic factors of one-carbon transfer pathways in frailty syndrome in older women./
Author:	Matteini, Amy Mahoney.
Description:	227 p.
Notes:	Adviser: M. Daniele Fallin.
Contained By:	Dissertation Abstracts International68-11B.
Subject:	Biology, Genetics. -
Online resource:	http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3288502
ISBN:	9780549312130

The role of nutritional and genetic factors of one-carbon transfer pathways in frailty syndrome in older women.
Matteini, Amy Mahoney.

The role of nutritional and genetic factors of one-carbon transfer pathways in frailty syndrome in older women. - 227 p.

Adviser: M. Daniele Fallin.

Thesis (Ph.D.)--The Johns Hopkins University, 2008.

The geriatric syndrome of frailty is characterized by physiologic vulnerability and loss of homeostasis arising from multiple biologic stressors.(Buchner and Wagner 1992; Fried and Walston 1999) Age-related declines in energy metabolism, neuroendocrine, musculoskeletal, and immunological systems are likely to contribute to the clinical characteristics of frailty.(Fried, Tangen et al. 2001; Bandeen-Roche, Xue et al. 2006) Mitochondrial dysfunction, increased oxidative stress and DNA damage have been hypothesized to contribute to the multi-system declines observed in frail older adults. (Walston, Hadley et al. 2006) Deficiencies in water-soluble vitamins B6, Biz and folate and mutations in one-carbon transfer-related genes trigger activation of inflammatory pathways via altered mitochondrial function, increased oxidative stress and resulting DNA damage, making one-carbon transfer pathways important targets for studying frailty. (Depeint, Bruce et al. 2006)

ISBN: 9780549312130Subjects--Topical Terms:

1017730
Biology, Genetics.

The role of nutritional and genetic factors of one-carbon transfer pathways in frailty syndrome in older women.
LDR:05581nam 2200325 a 45 001 856581
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020 $a 9780549312130
035 $a (UMI)AAI3288502
035 $a AAI3288502
040 $a UMI $c UMI
100 1 $a Matteini, Amy Mahoney. $3 1023405
245 1 4 $a The role of nutritional and genetic factors of one-carbon transfer pathways in frailty syndrome in older women.
300 $a 227 p.
500 $a Adviser: M. Daniele Fallin.
500 $a Source: Dissertation Abstracts International, Volume: 68-11, Section: B, page: 7224.
502 $a Thesis (Ph.D.)--The Johns Hopkins University, 2008.
520 $a The geriatric syndrome of frailty is characterized by physiologic vulnerability and loss of homeostasis arising from multiple biologic stressors.(Buchner and Wagner 1992; Fried and Walston 1999) Age-related declines in energy metabolism, neuroendocrine, musculoskeletal, and immunological systems are likely to contribute to the clinical characteristics of frailty.(Fried, Tangen et al. 2001; Bandeen-Roche, Xue et al. 2006) Mitochondrial dysfunction, increased oxidative stress and DNA damage have been hypothesized to contribute to the multi-system declines observed in frail older adults. (Walston, Hadley et al. 2006) Deficiencies in water-soluble vitamins B6, Biz and folate and mutations in one-carbon transfer-related genes trigger activation of inflammatory pathways via altered mitochondrial function, increased oxidative stress and resulting DNA damage, making one-carbon transfer pathways important targets for studying frailty. (Depeint, Bruce et al. 2006)
520 $a This project evaluated the cross-sectional relationship between nutritional and genetic factors related to one-carbon transfers and the frailty syndrome. First, associations between markers of vitamins availability, specifically elevated serum methylmalonic acid (MMA), homocysteine (tHcy), cystathionine and low folate, and frailty were described in 703 women from the Women's Health and Aging Studies (WHAS), complementary prospective cohorts of community-dwelling older women from Baltimore, Maryland. Next, a study of six candidate genes that influence onecarbon transfers was performed and associations between single nucleotide polymorphism (SNP) haplotypes, serum tHcy, MMA and frailty syndrome were evaluated in 415 WHAS women. We hypothesized that alterations in one-carbon transfer metabolism, induced by decreased vitamin availability and inherited genetic mutations, significantly contribute to frailty in older women.
520 $a Serum tHcy, MMA and cystathionine concentrations were observed to vary by race. On average, a higher proportion of Caucasian versus African American women was vitamin B12 deficient with higher MMA, while a greater proportion of African American versus Caucasian women had lower serum folate and higher tHcy and cystathionine concentrations. The prevalence of frailty was 19% in African Americans and 12% in Caucasians. Regardless of racial group, a one-interquartile range (IQR) increase in MMA was associated with 40-94% greater odds of binary frailty after adjustment for age, education, presence of cardiovascular disease (CVD) and renal impairment (ORCauc=1.39, 95%CI: 1.04-1.86; ORAA=1.94, 95%CI: 1.18-3.17). Elevated serum tHcy was also significantly associated with binary frailty after adjustment for age, education, CVD, renal impairment and elevated MMA in both groups (ORCauc=2.52, 95%CI: 1.05-6.06; ORAA=6.56, 95%CI: 2.14-20.12), although African American women exhibited 3 times greater odds than their Caucasian counterparts (p-value for interaction = 0.05). A significant relationship was also observed between elevated cystathionine and frailty syndrome in African Americans but not in Caucasians, after adjustment for age, education, CVD, renal impairment and elevated tHcy (ORAA=1.91, 95%CI: 1.36-10.13).
520 $a Fifty-six SNPs from CBS, MTHFR, MTR, MTRR, TCN1 and TCN2 genes were genotyped. CBS and TCN2 SNPs and haplotypes were significantly associated with serum tHcy variation among Caucasian women, after adjustment for age, elevated MMA, elevated cystathionine, low serum folate and renal impairment in linear regression models (multi-variane Wald p-values: CBS = 0.001; TCN2 = 0.002). Additionally, TCN2 polymorphisms, particularly one SNP reported to be in perfect linkage disequilibrium (LD) with functional variant Pro259Arg, were significantly associated with frailty syndrome in logistic regression models, after adjustment for age and elevated MMA (OR = 0.27, p-value = 0.009). There was no consistent association between SNPs and serum MMA.
520 $a These results suggest that vitamin deficiencies and genetic factors that influence remethylation via reduced vitamin B12 availability vary by race and may be important to frailty physiology in community-dwelling older women. Although more research is needed to characterize these relationships, vitamin supplementation is a safe, feasible intervention that may relieve not only some of the frailty burden, but may offer more global health benefits in older women. Further studies should focus on longitudinal characterization of these relationships and identification of functional polymorphisms underlying these associations.
590 $a School code: 0098.
650 4 $a Biology, Genetics. $3 1017730
650 4 $a Health Sciences, Epidemiology. $3 1019544
690 $a 0369
690 $a 0766
710 2 $a The Johns Hopkins University. $3 1017431
773 0 $t Dissertation Abstracts International $g 68-11B.
790 $a 0098
790 1 0 $a Fallin, M. Daniele, $e advisor
791 $a Ph.D.
792 $a 2008
856 4 0 $u http://pqdd.sinica.edu.tw/twdaoeng/servlet/advanced?query=3288502