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

Mark Lucock, Zoë Yates, Charlotte Martin, Jeong Hwa Choi, Lyndell Boyd, Sa Tang, Nenad Naumovski, Paul Roach, Martin Veysey

Research output: Contribution to journalArticle

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Abstract

Hydrogen sulphide (H2S) is a gaseous signalling molecule that regulates blood flow and pressure. It is synthesised from cysteine via cystathionine β-synthase and cystathionine γ-lyase. We examined whether thiol precursors of H2S, 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 H2S 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 B6 and B12, 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 γ-lyase and cystathionine β-synthase genes, respectively, are the biological determinants of H2S 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.

Original languageEnglish
Pages (from-to)221-229
Number of pages9
JournalGenes and Nutrition
Volume8
Issue number2
DOIs
Publication statusPublished - Mar 2013
Externally publishedYes

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Nutrigenomics
Hydrogen Sulfide
Sulfhydryl Compounds
Cysteine
Cystathionine
Blood Pressure
Hypertension
Population
Vitamin B Complex
Lyases
Vitamin B 6
Genotype
Phenotype
Folic Acid
Gasotransmitters
Genes
Retirement
Coenzymes
Homocysteine
Vitamin B 12

Cite this

Lucock, Mark ; Yates, Zoë ; Martin, Charlotte ; Choi, Jeong Hwa ; Boyd, Lyndell ; Tang, Sa ; Naumovski, Nenad ; Roach, Paul ; Veysey, Martin. / Hydrogen sulphide-related thiol metabolism and nutrigenetics in relation to hypertension in an elderly population. In: Genes and Nutrition. 2013 ; Vol. 8, No. 2. pp. 221-229.
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Hydrogen sulphide-related thiol metabolism and nutrigenetics in relation to hypertension in an elderly population. / Lucock, Mark; Yates, Zoë; Martin, Charlotte; Choi, Jeong Hwa; Boyd, Lyndell; Tang, Sa; Naumovski, Nenad; Roach, Paul; Veysey, Martin.

In: Genes and Nutrition, Vol. 8, No. 2, 03.2013, p. 221-229.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Hydrogen sulphide-related thiol metabolism and nutrigenetics in relation to hypertension in an elderly population

AU - Lucock, Mark

AU - Yates, Zoë

AU - Martin, Charlotte

AU - Choi, Jeong Hwa

AU - Boyd, Lyndell

AU - Tang, Sa

AU - Naumovski, Nenad

AU - Roach, Paul

AU - Veysey, Martin

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AB - Hydrogen sulphide (H2S) is a gaseous signalling molecule that regulates blood flow and pressure. It is synthesised from cysteine via cystathionine β-synthase and cystathionine γ-lyase. We examined whether thiol precursors of H2S, 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 H2S 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 B6 and B12, 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 γ-lyase and cystathionine β-synthase genes, respectively, are the biological determinants of H2S 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.

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KW - Hypertension

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