Hydrogen sulphide-related thiol metabolism and nutrigenetics in relation to hypertension in an elderly population

Abstract

Hydrogen sulphide (H 2 S) is a gaseous signalling molecule that regulates blood flow and pressure. It is synthesised from cysteine via cystathionine b-synthase and cystathionine c-lyase. We examined whether thiol precursors of H 2 S, transsulphuration pathway gene variants (CBS-844ins68 and CTH-G1364T) and key B-vitamin cofactors might be critical determinants of hypertension in an elderly Australian population. An elderly Australian retirement village population (n = 228; age 65-96 years, 91 males and 137 females) was assessed for the prevalence of two transsulphuration pathway-related variant genes associated with cysteine synthesis and hence H 2 S production. Thiols were determined by HPLC, genotypes by PCR and dietary intake by food frequency questionnaire. Homocysteine levels were statistically higher in the hypertensive phenotype (p = 0.0399), but there was no difference for cysteine or glutathione. Using nominal logistic regression, cysteine, CTH-G1364T genotype, dietary synthetic folate and vitamin B 6 predicted clinical phenotype (determined as above/below 140/90 mm Hg) and then only in female subjects (p = 0.0239, 0.0178, 0.0249 and 0.0371, respectively). Least-squares regression supports cysteine being highly inversely predictive of diastolic blood pressure: p and r 2 values \0.0001 and 0.082; 0.0409 and 0.046; and \0.0001 and 0.113 for all subjects, males and females, respectively. Additionally, CTH-G1364T genotype predicts diastolic blood pressure in males (p = 0.0217; r 2 = 0.083), but contrasts with observations for females. Overall, analyses, including stepwise regression, suggest cysteine, dietary natural and synthetic folate, vitamins B 6 and B 12 , and both genetic variants (CTH-C1364T and CBS-844ins68) are all aetiologically relevant in the regulation of blood pressure. Hydrogen sulphide is a vasorelaxant gasotransmitter with characteristics similar to nitric oxide. Cysteine and the G1364T and 844ins68 variants of the cystathionine c-lyase and cystathionine b-synthase genes, respectively, are the biological determinants of H 2 S synthesis, and all three are shown here to influence the hypertensive phenotype. Additionally, B-vitamin cofactors for these three enzymes may also be important determinants of blood pressure.

Electrocardiogram Derived QRS Duration >120 ms is Associated With Elevated Plasma Homocysteine Levels in a Rural Australian Cross-Sectional Population

“… 14 Our mean population homocysteine levels (10.4 μmol/L) are slightly higher than a New South Wales (NSW) Central Coast aged cohort (9.39 μmol/L), where a significant proportion of the participants were hypertensive. 16 Logistic models in the NSW Central Coast study did not reveal a significant interaction with blood pressure and homocysteine levels. 16 We found that a previous history of hypertension influenced QRS duration (the primary outcome measure) in our studies, although when modeled as an interactive factor in regression models (with age and gender), the association with homocysteine and QRS duration was reduced.…”

“… 16 Logistic models in the NSW Central Coast study did not reveal a significant interaction with blood pressure and homocysteine levels. 16 We found that a previous history of hypertension influenced QRS duration (the primary outcome measure) in our studies, although when modeled as an interactive factor in regression models (with age and gender), the association with homocysteine and QRS duration was reduced. On the other hand, our subgroup consisted of only 21 participants with a QRS duration >120 ms, therefore we cautiously report our adjustments with respect to demographic clinical history in regression models and do not overstate their significance.…”

Emerging role of hydrogen sulfide in hypertension and related cardiovascular diseases

“…Therefore, the true effect of CSE deficiency on BP remains unclear at present. Lucock et al found that both genetic variants of CSE-G1364T and CBS-844ins68 are biological determinants of H2S synthesis and are aetiologically important in the regulation of BP (Lucock et al, 2013). In addition, it has been observed that mean arterial pressure (MAP) in rats is not enhanced after treatment with either the CSE inhibitor DL-propargylglycine (PAG) or the CBS inhibitor aminooxyacetic acid (AOA) alone for 4 weeks; however, MAP increased gradually from 99 ± 2 to 130 ± 1 mmHg during 4 weeks of treatment with the combination of PAG and AOA (Roy et al, 2012).…”

Association between Hcy levels and the CBS844ins68 and MTHFR C677T polymorphisms with essential hypertension

“…The mutation causes CBS metabolic activity to decrease and affects the metabolism of Hcy. Previous studies have shown that the CBS844ins68 gene polymorphisms exist in different populations; the frequency of the insertion (I) allele was 10% in Britian, 7% in Pakistan and 1.4% in the Henan Han population (7)(8)(9). Thus far, the correlation of the CBS844ins68 gene polymorphism and EH is rarely reported in domestic and foreign countries.…”