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Folate network genetic variation predicts cardiovascular disease risk in non-Hispanic white males.

ABSTRACT: Genes functioning in folate-mediated 1-carbon metabolism are hypothesized to play a role in cardiovascular disease (CVD) risk beyond the current narrow focus on the MTHFR 677 C?T (rs1801133) polymorphism. Using a cohort study design, we investigated whether sequence variants in the network of folate-related genes, particularly in genes encoding proteins related to SHMT1, predict CVD risk in 1131 men from the Normative Aging Study. A total of 330 single nucleotide polymorphisms (SNPs) in 52 genes, selected for function and gene coverage, were assayed on the Illumina GoldenGate platform. Age- and smoking-adjusted genotype-phenotype associations were estimated in regression models. Using a nominal P ? 5.00 × 10(-3) significance threshold, 8 SNPs were associated with CVD risk in single locus analyses. Using a false discovery rate (FDR) threshold (P-adjusted ?1.00 × 10(-1)), a SNP in the GGH gene remained associated with reduced CVD risk, with a stronger association in early onset CVD cases (<55 y). A gene × folate interaction (MAT2B) and 2 gene × vitamin B-12 interactions (BHMT, SLC25A32) reached the FDR P-adjusted ?2.00 × 10(-1) threshold. Three biological hypotheses related to SHMT1 were explored and significant gene × gene interactions were identified for TYMS by UBE2N, FTH1 by CELF1, and TYMS by MTHFR. Variations in genes other than MTHFR and those directly involved in homocysteine metabolism are associated with CVD risk in non-Hispanic white males. This work supports a role for SHMT1-related genes and nuclear folate metabolism, including the thymidylate biosynthesis pathway, in mediating CVD risk.

SUBMITTER: Wernimont SM

PROVIDER: S-EPMC3374665 | biostudies-literature | 2012 Jul

REPOSITORIES: biostudies-literature

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Folate network genetic variation predicts cardiovascular disease risk in non-Hispanic white males.

Wernimont Susan M SM Clark Andrew G AG Stover Patrick J PJ Wells Martin T MT Litonjua Augusto A AA Weiss Scott T ST Gaziano J Michael JM Vokonas Pantel S PS Tucker Katherine L KL Cassano Patricia A PA

The Journal of nutrition 20120530 7

Genes functioning in folate-mediated 1-carbon metabolism are hypothesized to play a role in cardiovascular disease (CVD) risk beyond the current narrow focus on the MTHFR 677 C→T (rs1801133) polymorphism. Using a cohort study design, we investigated whether sequence variants in the network of folate-related genes, particularly in genes encoding proteins related to SHMT1, predict CVD risk in 1131 men from the Normative Aging Study. A total of 330 single nucleotide polymorphisms (SNPs) in 52 genes ...[more]

PMID: 22649255

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Project description:IntroductionThe study evaluated if blood markers reflecting diverse biological pathways differentiate clinical diagnostic groups among Hispanic and non-Hispanic White adults.MethodsWithin Hispanic (n = 1193) and non-Hispanic White (n = 650) participants, serum total tau (t-tau), neurofilament light (NfL), ubiquitin carboxyl-terminal hydrolase LI, glial fibrillary acidic protein (GFAP), soluble cluster of differentiation-14, and chitinase-3-like protein 1 (YKL-40) were quantified. Mixed-effects partial proportional odds ordinal logistic regression and linear mixed-effects models were used to evaluate the association of biomarkers with diagnostic group and cognition, adjusting for age, sex, ethnicity, apolipoprotein E ε4, education, and site.ResultsT-tau, NfL, GFAP, and YKL-40 discriminated between diagnostic groups (receiver operating curve: 0.647-0.873). Higher t-tau (odds ratio [OR] = 1.671, 95% confidence interval [CI] = 1.457-1.917, P < .001), NfL (OR = 2.150, 95% CI = 1.819-2.542, P < .001), GFAP (OR = 2.283, 95% CI = 1.915-2.722, P < .001), and YKL-40 (OR = 1.288, 95% CI = 1.125-1.475, P < .001) were associated with increased likelihood of dementia relative to cognitively unimpaired and mild cognitive impairment groups. Higher NfL was associated with poorer global cognition (β = -0.455, standard error [SE] = 0.083, P < .001), semantic fluency (β = -0.410, SE = 0.133, P = .002), attention/processing speed (β = 2.880, SE = 0.801, P < .001), and executive function (β = 5.965, SE = 2.037, P = .003). Higher GFAP was associated with poorer global cognition (β = -0.345, SE = 0.092, P = .001), learning (β = -1.426, SE = 0.359, P < .001), and memory (β = -0.890, SE = 0.266, P < .001). Higher YKL-40 (β = -0.537, SE = 0.186, P = .004) was associated with lower memory scores. Interactions with ethnicity were observed for learning (NfL, GFAP, YKL-40), memory (NfL, GFAP), and semantic fluency (NfL; interaction terms P < .008), which were generally no longer significant in a demographically matched subset of Hispanic and non-Hispanic White participants.DiscussionBlood biomarkers of neuronal/axonal and glial injury differentiated between clinical diagnostic groups in a bi-ethnic cohort of Hispanic and non-Hispanic Whites. Our results add to the growing literature indicating that blood biomarkers may be viable tools for detecting neurodegenerative conditions and highlight the importance of validation in diverse cohorts.

Project description:OBJECTIVE:Research suggests a difference in sweet taste perception between non-Hispanic black (NHB) and non-Hispanic white (NHW) adults; however, limited research has examined sweet taste perception in relation to the dietary intake of sweet products. The aim of this study was to examine sweet taste perception and the consumption of sweet foods, beverages, and sugar in NHB and NHW adults, and to evaluate whether sweet taste perception is associated with dietary intake. METHODS:This cross-sectional study examined the association between race, sweet taste perception and sweet food, beverages, and sugar consumption in healthy, NHB and NHW adults. Seven day food records were analyzed in Nutrition Data System for Research software. Intensity of sweet taste perception was tested and the general labeled magnitude scale method was used to facilitate group comparisons. Independent t tests, Mann-Whitney tests, and Pearson correlations were used to assess associations. RESULTS:Participants were NHB (n?=?98) and NHW (n?=?90) adults, 41 ± 1 y of age (mean ± SEM) with energy intake of 2271 ± 53 kcal. Body mass index was higher in NHBs than in NHWs (36 ± 1 versus 32 ± 1 kg/m2, P?=?0.048), but no differences were observed in age, energy consumption, or total sugar intake. Sweet taste perception rating (median [interquartile range] NHB: 73.5 [63.9-83], NHW: 52.1 [46.4-57.7]; P?=?0.001) and added sugar intake (NHB: 39.4 g/1000 kcal [36.3-42.4], NHW: 30 g/1000 kcal [26.7-33.4]; P < 0.001) were greater in NHB. Perceived sweet taste intensity was positively associated with consumption of servings of sweet products among NHBs (R2?=?0.057, P?=?0.018) but not NHWs (R2?=?-0.012, P?=?0.314). CONCLUSIONS:NHBs have a higher intensity of sweet taste perception than NHWs. The positive association of sweet taste perception and sweet product consumption in NHBs suggests that a higher intensity of sweet taste perception may be associated with an increased proportion of energy consumption from added sugars.

Dataset Information

Folate network genetic variation predicts cardiovascular disease risk in non-Hispanic white males.

Publications

Folate network genetic variation predicts cardiovascular disease risk in non-Hispanic white males.

Similar Datasets

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