Genes & Nutrition

, Volume 8, Issue 2, pp 221–229 | Cite as

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 Paper

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 B6 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 r2 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; r2 = 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.

Keywords

Hydrogen sulphide Cystathionine γ-lyase Cysteine Homocysteine Hypertension Cystathionine β-synthase B-vitamins 

References

  1. Boushey CJ, Beresford SA, Omenn GS, Motulsky AG (1995) A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. Probable benefits of increasing folic acid intakes. JAMA 274:1049–1057PubMedCrossRefGoogle Scholar
  2. Bucci M, Mirone V, Di Lorenzo A, Vellecco V, Roviezzo F, Brancaleone V, Ciro I, Cirino G (2009) Hydrogen sulphide is involved in testosterone vascular effect. Eur Urol 56:378–383PubMedCrossRefGoogle Scholar
  3. Doshi S, McDowell I, Moat S, Lewis M, Goodfellow J (2003) Folate improves endothelial function in patients with coronary heart disease. Clin Chem Lab Med 41:1505–1512PubMedCrossRefGoogle Scholar
  4. Dufficy L, Naumovski N, Ng X, Blades B, Yates Z, Travers C, Lewis P, Sturm J, Veysey M, Roach PD, Lucock MD (2006) G80A reduced folate carrier SNP influences the absorption and cellular translocation of dietary folate and its association with blood pressure in an elderly population. Life Sci 79:957–966PubMedCrossRefGoogle Scholar
  5. Elliott WJ (2005) Cardiovascular events in hypertension trials of Angiotensin-converting enzyme inhibitors. J Clin Hypertens 7:2–4CrossRefGoogle Scholar
  6. Gadalla MM, Snyder SH (2010) Hydrogen sulfide as a gasotransmitter. J Neurochem 113:14–26PubMedCrossRefGoogle Scholar
  7. Gupta YK, Dahiya AK, Reeta KH (2010) Gaso-transmitter hydrogen sulphide: potential new target in pharmacotherapy. Indian J Exp Biol 48:1069–1077PubMedGoogle Scholar
  8. Hayden MR, Tyagi SC (2004) Homocysteine and reactive oxygen species in metabolic syndrome, type 2 diabetes mellitus, and atheroscleropathy: the pleiotropic effects of folate supplementation. Nutr J 3:4PubMedCrossRefGoogle Scholar
  9. Hyndman ME, Verma S, Rosenfeld RJ, Anderson TJ, Parsons HG (2002) Interaction of 5-methyltetrahydrofolate and tetrahydrobiopterin on endothelial function. Am J Physiol Heart Circ Physiol 282:2167–2172Google Scholar
  10. Inoue R, Ohkubo T, Kikuya M, Metoki H, Asayama K, Obara T, Hirose T, Hara A, Hoshi H, Hashimoto J, Totsune K, Satoh H, Kondo Y, Imai Y (2007) Stroke risk in systolic and combined systolic and diastolic hypertension determined using ambulatory blood pressure the ohasama study. Am J Hypertens 20:1125–1131PubMedCrossRefGoogle Scholar
  11. Kearney PM, Whelton M, Reynolds K, Muntner P, Whelton PK, He J (2005) Global burden of hypertension: analysis of worldwide data. Lancet 365:217–223PubMedGoogle Scholar
  12. Li Y, Zhao Q, Liu XL, Wang LY, Lu XF, Li HF, Chen SF, Huang JF, Gu DF (2008) Relationship between cystathionine gamma-lyase gene polymorphism and essential hypertension in Northern Chinese Han population. Chin Med J 121:716–720PubMedGoogle Scholar
  13. Lucock M (2000) Folic acid: nutritional biochemistry, molecular biology, and role in disease processes. Mol Genet Metab 71:121–138PubMedCrossRefGoogle Scholar
  14. Lucock MD (2006) Synergy of genes and nutrients: the case of homocysteine. Curr Opin Clin Nutr Metab Care 9:748–756PubMedCrossRefGoogle Scholar
  15. Lucock M, Yates Z, Boyd L, Naylor C, Choi JH, Ng X, Skinner V, Wai R, Kho J, Tang S, Roach P, Veysey M (2012) Vitamin C-related nutrient–nutrient and nutrient-gene interactions that modify folate status. Eur J Nutr (In Press)Google Scholar
  16. Moat SJ, Lang D, McDowell IFW, Clarke ZL, Madhavan AK, Lewis MJ, Goodfellow J (2004) Folate, homocysteine, endothelial function and cardiovascular disease. J Nutr Biochem 15:64–79PubMedCrossRefGoogle Scholar
  17. National Cholesterol Education Program Expert Panel (2002) Expert panel on detection, evaluation and treatment of high blood cholesterol in adults: third report of the national cholesterol education program (NCEP) expert panel on detection, evaluation and treatment of high blood cholesterol in adults (Adult Treatment Panel III). Circulation 106:3143–3421Google Scholar
  18. Nygard O, Nordrehaug JE, Refsum H, Ueland PM, Farstad M, Vollset SE (1997) Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 337:230–236PubMedCrossRefGoogle Scholar
  19. Paoletti E, Bellino D, Amidone M, Rolla D, Cannella G (2006) Relationship between arterial hypertension and renal damage in chronic kidney disease: insights from ABPM. J Nephrol 19:778–782PubMedGoogle Scholar
  20. Parnetti L, Caso V, Santucci A, Corea F, Lanari A, Floridi A, Conte C, Bottiglieri T (2004) Mild hyperhomocysteinemia is a risk-factor in all etiological subtypes of stroke. Neurol Sci 25:13–17PubMedCrossRefGoogle Scholar
  21. Reynolds K, Gu D, Muntner P, Kusek JW, Chen J, Wu X et al (2007) A population-based, prospective study of blood pressure and risk for end-stage renal disease in china. J Am Soc Nephrol 18:1928–1935PubMedCrossRefGoogle Scholar
  22. Schultz HD, Li YL, Ding Y (2007) Arterial chemoreceptors and sympathetic nerve activity: implications for hypertension and heart failure. Hypertension 50:6–13PubMedCrossRefGoogle Scholar
  23. Singh S, Padovani D, Leslie RA, Chiku T, Banerjee R (2009) Relative contributions of cystathionine beta-synthase and gamma-cystathionase to H2S biogenesis via alternative trans-sulfuration reactions. J Biol Chem 284:22457–22466PubMedCrossRefGoogle Scholar
  24. Stroes ES, van Faassen EE, Yo M, Martasek P, Boer P, Govers R, Rabelink TJ (2000) Folic acid reverts dysfunction of endothelial nitric oxide synthase. Circ Res 86:1129–1134PubMedCrossRefGoogle Scholar
  25. Sutton-Tyrrell K, Bostom A, Selhub J, Zeigler-Johnson C (1997) High homocysteine levels are independently related to isolated systolic hypertension in older adults. Circulation 96:1745–1749PubMedCrossRefGoogle Scholar
  26. Tsai MY, Bignell M, Schwichtenberg K, Hanson NQ (1996) High prevalence of a mutation in the cystathionine beta-synthase gene. Am J Hum Genet 59:1262–1267PubMedGoogle Scholar
  27. Wagner CA (2009) Hydrogen sulfide: a new gaseous signal molecule and blood pressure regulator. J Nephrol 22:173–176PubMedGoogle Scholar
  28. Yang G, Wu L, Jiang B, Yang W, Qi J, Cao K, Meng Q, Mustafa AK, Mu W, Zhang S, Snyder SH, Wang R (2008) H2S as a physiologic vasorelaxant: hypertension in mice with deletion of cystathionine gamma-lyase. Science 322:587–590PubMedCrossRefGoogle Scholar
  29. Zhou J, Moller J, Danielson CC, Bentzon J, Ravn HB, Austin RC, Falk E (2001) Dietary supplementation with methionine and homocysteine promotes early atherosclerosis but not plaque rupture in ApoE-deficient mice. Arterioscler Thromb Vasc Biol 21:1470–1476PubMedCrossRefGoogle Scholar
  30. Zylberstein DE, Bengtsson C, Bjorkelund C, Landaas S, Sundh V, Thelle D, Lissner L (2004) Serum homocysteine in relation to mortality and morbidity from coronary heart disease: a 24-year follow-up of the population study of women in Gothenburg. Circulation 109:601–606PubMedCrossRefGoogle Scholar

Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Mark Lucock
    • 1
  • Zoë Yates
    • 1
  • Charlotte Martin
    • 1
  • Jeong-Hwa Choi
    • 1
  • Lyndell Boyd
    • 1
  • Sa Tang
    • 1
  • Nenad Naumovski
    • 1
  • Paul Roach
    • 1
  • Martin Veysey
    • 2
  1. 1.School of Environmental and Life SciencesUniversity of NewcastleOurimbahAustralia
  2. 2.Teaching and Research UnitCentral Coast Local Health DistrictGosfordAustralia

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