BackgroundElevated homocysteine (Hcy) is associated with several pathologies. Gene–diet interactions related to Hcy might be used to customize dietary advice to reduce disease incidence. To explore this possibility, we investigated interactions between anthropometry, biochemical markers and diet and single-nucleotide polymorphisms (SNPs) in relation to Hcy concentrations. Five SNPs of Hcy-metabolizing enzymes were analyzed in 2010 black South Africans.ResultsHcy was higher with each additional methylenetetrahydrofolate reductase (MTHFR) C677T minor allele copy, but was lower in methionine synthase (MTR) 2756AA homozygotes than heterozygotes. Individuals harboring cystathionine β synthase (CBS) 833 T/844ins68 had lower Hcy concentrations than others. No interactive effects were observed with any of the anthropometrical markers. MTHFR C677T and CBS T833C/844ins68 homozygote minor allele carriers presented with lower Hcy as high density lipoprotein cholesterol (HDL-c) increased. Hcy concentrations were negatively associated with dietary protein and animal protein intake in the TT and TC genotypes, but positively in the CC genotype of CBS T833C/844ins68. Hcy was markedly higher in TT homozygotes of MTHFR C677T as added sugar intake increased. In CBS T833C/844ins68 major allele carriers, biotin intake was negatively associated with Hcy; but positively in those harboring the homozygous minor allele.ConclusionsThe Hcy–SNP associations are modulated by diet and open up the possibility of invoking dietary interventions to treat hyperhomocysteinemia. Future intervention trials should further explore the observed gene–diet and gene–blood lipid interactions.
Elevated homocysteine (Hcy) increases cardiovascular disease (CVD) risk. Our objective was to emphasize Hcy’s contribution in hypertension and CVD management by determining H-type hypertension (hypertension with Hcy ≥ 10 µmol/L) and associations between Hcy, blood pressure (BP) and estimates of vascular function among Black South Africans. We included 1995 adults (63% female). Plasma Hcy and cardiovascular measures (systolic and diastolic BP (SBP, DBP), pulse pressure, heart rate (HR), carotid-radialis pulse wave velocity (cr-PWV), intercellular adhesion molecule-1 (ICAM-1) and vascular cell adhesion molecule-1) were quantified. Five Hcy-related polymorphisms (cystathionine β-synthase (CBS 844ins68, T833C, G9276A); methylenetetrahydrofolate reductase (MTHFR C677T) and methionine synthase (MTR A2756G)) were genotyped. Hcy was >10 µmol/L in 41% (n = 762), and of the 47% (n = 951) hypertensives, 45% (n = 425) presented with H-type. Hcy was higher in hypertensives vs. normotensives (9.86 vs. 8.78 µmol/L, p < 0.0001, effect size 0.56) and correlated positively with SBP, DBP, cr-PWV and ICAM-1 (r > 0.19, p < 0.0001). Over Hcy quartiles, SBP, DBP, HR, cr-PWV and ICAM-1 increased progressively (all p-trends ≤ 0.001). In multiple regression models, Hcy contributed to the variance of SBP, DBP, HR, cr-PWV and ICAM-1. H-type hypertensives also had the lowest MTHFR 677 CC frequency (p = 0.03). Hcy is positively and independently associated with markers of vascular function and raised BP.
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