Skip to content
Licensed Unlicensed Requires Authentication Published by De Gruyter September 21, 2011

Serum homocysteine levels and paraoxonase 1 activity in preschool aged children in Greece

  • George A. Karikas , Anastasios Kriebardis , Ioanna Samara , Kleopatra Schulpis , Maria Papachristodoulou and Athena Fytou-Pallikari

Abstract

Background: Over the past decade, it has been well established that elevated total serum homocysteine (tHcy) in adults is associated with increased risk of cardiovascular and thromboembolic diseases. Since risk factors for such diseases are established at a young age, the aim of the present study was to measure serum tHcy levels in 134 (71 boys, 63 girls) randomly selected healthy preschool children aged 4–6years (mean 5.1), and to investigate possible correlation with paraoxonase 1 (PON1) activity, an antioxidant enzyme that contributes to the antiatherogenic properties of high-density lipoprotein (HDL).

Methods: tHcy was determined using an IMX tHcy assay (FPIA). PON1 was measured by a spectrophotometric method at 412nm.

Results: Mean serum tHcy was 7.71±2.35μmol/L. A relatively significant percentage (15.6%) of boys and girls had elevated serum tHcy levels (>10μmol/L). tHcy levels were slightly higher in girls compared to boys (8.20±2.80 vs. 7.29±1.79μmol/L, respectively; p<0.11). There was no significant interaction between age and tHcy levels. Mean PON1 activity was 124.86±66.62U/L. No statistical difference in enzyme activity was observed between boys and girls (126.81±69.99 vs. 121.74±64.78U/L) was observed. On the contrary, a weak negative relationship between tHcy concentration and PON1 activity was detected, with Pearson's correlation coefficient of r=−0.27.

Conclusions: The significant percentage of elevated tHcy levels observed in healthy preschool cases and the negative tHcy correlation with PON1 activity are reported for the first time. Since children with a family history of cardiovascular disease have higher levels of serum Hcy, tHcy screening in children, even of this age, in relation to other parameters, such the protective PON1, might prove a useful prevention procedure for the genetic risk of premature atherosclerosis.


Corresponding author: Dr. G.A. Karikas, TEI-A, Ag. Spiridonos St., Egaleo 12210, Athens, Greece Phone/Fax: +30-210-5385629,

References

1. Malinow MR, Kang SS, Taylor LM, Wong PW. Prevalence I hyperhomocysteinemia in patients with peripheral arterial occlusive disease. Circulation 1989; 79:1180–8.10.1161/01.CIR.79.6.1180Search in Google Scholar

2. McCully KS. Vascular pathology of homocysteinemia: implications for the pathogenesis of arteriosclerosis. Am J Pathol 1969; 56:111–28.Search in Google Scholar

3. Bouchey CJ, Beresford SA, Omenn GS, Motulsky AG. A quantitative assessment of plasma homocysteine as a risk factor for vascular disease. J Am Med Assoc 1995; 274:1049–57.10.1001/jama.1995.03530130055028Search in Google Scholar PubMed

4. The European Concerted Action Project. Plasma homocysteine as a risk factor for vascular disease. J Am Med Assoc 1997;277:1775–81.10.1001/jama.1997.03540460039030Search in Google Scholar PubMed

5. Nygard O, Nordrehang JE, Refsum H, Ueland PM, Farstad M, Vollset SE. Plasma homocysteine levels and mortality in patients with coronary artery disease. N Engl J Med 1997; 337:230–6.10.1056/NEJM199707243370403Search in Google Scholar PubMed

6. Frosst P, Blom HJ, Milos R. A candidate genetic risk factor for vascular disease: a common mutation in methylenetetrahydrofolate reductase. Nat Genet 1995; 10:111–3.10.1038/ng0595-111Search in Google Scholar PubMed

7. Delvin EE, Rosen R, Merouani A, Genest J, Lambert M. Influence of MTHFR genotype, age, vitamin B12 and folate status on plasma homocysteine in children. Am J Clin Nutr 2000; 72:1469–73.10.1093/ajcn/72.6.1469Search in Google Scholar PubMed

8. van der Mooren MJ, Wouters MG, Blom HJ, Schellekens LA, Eskes TK, Rolland R. Hormone replacement therapy may reduce high serum homocysteine in postmenopausal women. Eur J Clin Invest 1994; 24:733–6.10.1111/j.1365-2362.1994.tb01069.xSearch in Google Scholar PubMed

9. Schulpis KH, Karikas GA, Papakonstantinou E. Homocysteine and other vascular risk factors in patients with phenylketonuria on a diet. Acta Paediatr 2002; 91:905–9.10.1111/j.1651-2227.2002.tb02853.xSearch in Google Scholar

10. Osganian SK, Stampfer MJ, Spiegelman D, Rimm E, Cutler JA, Feldmam HA, et al. Distribution of and factors associated with serum Hcy levels in children: Child and Adolescent Trial for Cardiovascular Health. J Am Med Assoc 1999; 281:1189–96.10.1001/jama.281.13.1189Search in Google Scholar PubMed

11. Tonstad S, Refsum H, Sivertsen M, Christophersen B, Ose L, Ueland PM. Relation of total homocysteine and lipid levels in children to premature cardiovascular death in male relatives. Pediatr Res 1996; 40:47–52.10.1203/00006450-199607000-00009Search in Google Scholar PubMed

12. Vilaseca MA, Moyano D, Ferrer I, Artuch R. Total Hcy in pediatric patients. Clin Chem 1997; 43:690–2.10.1093/clinchem/43.4.690Search in Google Scholar

13. Kahn A. Plasma Hcy concentration in a Belgian school-age population. Am J Clin Nutr 1999;69:968–72.10.1093/ajcn/69.5.968Search in Google Scholar PubMed

14. Must A, Jacques PF, Rogers G, Rosemberg IH, Selhub J. Serum total homocysteine concentrations in children and adolescents: results from the Third National Health and Nutrition Examination Survey (NHANES III). J Nutr 2003; 133:2643–9.10.1093/jn/133.8.2643Search in Google Scholar PubMed

15. Valabhji J, McCall AJ, Schachter M, Dhanjil S, Richmond W, Elkeles RS. High density lipoprotein composition and paraoxonase activity in type I diabetes. Clin Sci 2001; 101:659–70.10.1042/CS20010111Search in Google Scholar

16. Mackness B, Durrington PN, Boulton AJ, Hine D, Mackness MI. Serum paraoxonase activity in patients with type I diabetes compared to healthy controls. Eur J Clin Invest 2002; 32:259–64.10.1046/j.1365-2362.2002.00977.xSearch in Google Scholar PubMed

17. Durrington PN, Mackness B, Mackness MI. Paraoxonase and atherosclerosis. Arterioscler Thromb Vasc Biol 2001; 21:473–80.10.1161/01.ATV.21.4.473Search in Google Scholar PubMed

18. Jakubowski H. Calcium-dependent human serum homocysteine thiolactone hydrolase. J Biol Chem 2000; 275:3957–62.10.1074/jbc.275.6.3957Search in Google Scholar PubMed

19. Rosenblat M, Grunfeld O, Hayek T, Aviram M. Serum paraoxonase activity and the extent of lipid peroxidation are not affected by increased levels of human apolipoprotein A-I: studies in transgenic mice. Clin Chem Lab Med 2002; 40:9–14.10.1515/CCLM.2002.003Search in Google Scholar PubMed

20. Pernet P, Lasnier E, Vaubourdolle M. Evaluation of the AxSYM homocysteine assay and comparison with the IMX homocysteine assay. Clin Chem 2000; 46:1440–1.10.1093/clinchem/46.9.1440Search in Google Scholar

21. Chimonas ET. The treatment of coronary heart disease; an update. Part 2. Mortality trends and main causes of death in the Greek population. Curr Med Res Opin 2001; 17:27–33.10.1185/03007990152005315Search in Google Scholar

22. Ueland PM, Borke Monsen AL. Hyperhomocysteinemia and B-vitamin deficiencies in infants and children. Clin Chem Lab Med 2003; 41:1418–26.Search in Google Scholar

23. Bates CJ, Mansoor MA, Gregory J, Pentiev K, Prentice A. Correlates of plasma homocysteine, cysteine and cysteinyl-glycine in respondents in the British National Diet and Nutrition Survey of young people aged 4–18 years, and a comparison with the survey of people aged 65 years and over. Br J Nutr 2002; 87:71–9.10.1079/BJN2001479Search in Google Scholar

24. Refsum H, Grindflek AW, Ueland PM, Fredriksen E, Meyer K, Ulvik A, et al. Screening for serum total homocysteine in newborn children. Clin Chem 2004; 50:1769–84.10.1373/clinchem.2004.036194Search in Google Scholar

25. Reddy MN. Reference ranges for total homocysteine in children. Clin Chim Acta 1997; 262:153–5.10.1016/S0009-8981(97)06548-0Search in Google Scholar

26. De Laet C, Wautrecht JC, Brasseur D, Dramaix M, Boeynaems JM, Decuyper J, et al. Plasma homocysteine concentration in a Belgian school-age population. Am J Clin Nutr 1999; 69:968–72.10.1093/ajcn/69.5.968Search in Google Scholar PubMed

27. Tonstad S, Refsum H, Ueland PM. Association between plasma total homocysteine and parental history of cardiovascular disease in children with familial hypercholesterolemia. Circulation 1997; 96:1803–8.10.1161/01.CIR.96.6.1803Search in Google Scholar

28. Dedousis GV, Panagiotakos DB, Chrysohoou C, Pitsavos C, Zampelas A, Choumerianou D, et al. Effect of interaction between adherence to a Mediterranean diet and the methylenetetrahydrofolate reductase 677C>T mutation on homocysteine concentrations in healthy adults: the ATTICA Study. Am J Clin Nutr 2004; 80:849–54.10.1093/ajcn/80.4.849Search in Google Scholar PubMed

29. Papoutsakis C, Yiannakouris N, Manios Y, Papaconstantinou E, Magkos F, Schulpis KH, et al. Plasma homocysteine concentrations in Greek children are influenced by an interaction between the methylenetetrahdrofolate reductase C677T genotype and folate status. J Nutr 2005; 135:383–8.10.1093/jn/135.3.383Search in Google Scholar PubMed

30. Kark JD, Sinnreich R, Rosenberg IH, Jacques PF, Selhub J. Plasma homocysteine and parental myocardial infarction in young adults in Jerusalem. Circulation 2002; 105:2725–9.10.1161/01.CIR.0000017360.99531.26Search in Google Scholar PubMed

31. Hogeveen M, Blom HJ, Van Amerongen M, Boogmans B, Van Beynum IM, Van De Bor M. Hyperhomocysteinemia as risk factor for ischemic and hemorrhagic stroke in new-born infants. J Pediatr 2002; 141:429–31.10.1067/mpd.2002.126598Search in Google Scholar PubMed

Received: 2005-12-29
Accepted: 2006-2-13
Published Online: 2011-9-21
Published in Print: 2006-5-1

©2006 by Walter de Gruyter Berlin New York

Downloaded on 30.4.2024 from https://www.degruyter.com/document/doi/10.1515/CCLM.2006.110/html
Scroll to top button