Citation Information :
Kamble CG, Hisalkar P, Padhyegurjar SB, Powar JD, Jagdale BV. Study of Serum Homocysteine Level Variations in Sickle Cell Disease: A Meta-analysis Study. Indian J Med Biochem 2020; 24 (3):104-114.
Background: Serum homocysteine levels have been observed to be increased in sickle cell disease (SCD). The biological mechanism of synthesis and regulation of the homocysteine remains unclear. This meta-analysis aims to provide an overview of the serum homocysteine level changes and to discuss its significance in SCD.
Materials and methods: This meta-analysis is to determine serum homocysteine level changes during SCD and was conducted under the PRISMA guidelines. Without language restrictions, the articles were identified through BioMed, Embase, Pub Med® (U.S. National Library of Medicine, USA), and www.Blood Journal.org, PLoS ONE, Web of Science, LILACS (Latin American and Caribbean Health Sciences Literature), ISI Web of Science, Chemical abstract services-(CAS), Europe PMC, Bio sis Previews, Elsevier Properties S.A., USA. The studies have been considered which were published before March 31, 2018.
Results: Thirty comparative studies were identified out of 8,630 articles and included in the meta-analysis. From the final selected articles, the mean, standard deviation, sample size of cases vs controls were showing compared and calculated by the SPSS latest software version-24. From 30, 18 articles were statistically highly significant, and the remaining 12 articles were statistically not significant. The p <0.05 was considered to be statistically significant. The combined estimation of the meta-analysis study is highly significant, since p <0.000000, calculated “t” is 25.07, and degree of freedom is 2,829.
Conclusion: The study concludes that there is an extremely significant difference between mean serum homocysteine levels in cases and healthy controls. So, the serum homocysteine level can be used as a clinical biomarker for the diagnosis of SCD.
Modell B, Darlison M, Birgens H, et al. Epidemiology of haemoglobin disorders in Europe: an overview. Scand J Clin Lab Invest 2007;67(1):39–69. DOI: 10.1080/00365510601046557.
Akinyanju OO. Profile of sickle cell disease in Nigeria. Ann NY Acad Sci 1989;565(1 Sickle Cell D):126–136. DOI: 10.1111/j.1749-6632.1989.tb24159.x. https://www.ncbi.nlm.nih.gov/pubmed/2672962.
Ballas SK. The sickle cell painful crisis in adults: phases and objective signs. Hemoglobin 1995;19(6):323–333. DOI: 10.3109/03630269509005824. https://www.ncbi.nlm.nih.gov/pubmed/8718691.
Van der Dijs FPL, Fokkema MR, Brouwer DA, et al. Optimization of folic acid, vitamin B12 and vitamin B6 supplements in pediatric patients with sickle cell disease. Am J Hematol 2002;69:239–246. DOI: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.10083.
Bialecka M, Robowski P, Honczarenko K, et al. Genetic and environmental factors for hyperhomocysteinaemia and its clinical implications in Parkinson's disease. J Neurologia Polska 2009;43:272–285. http://europepmc.org/abstract/med/19618311.
Lowenthal EA, Mayo MS, Cornwell PE, et al. Homocysteine elevation in sickle cell disease. J Am Coll Nutrit 2000;19(5):608–612. DOI: 10.1080/07315724.2000.10718958. https://www.ncbi.nlm.nih.gov/pubmed/11022874.
Balasa VV, Kalinyak KA, Bean JA, et al. Hyperhomocysteinemia is associated with low plasma pyridoxine levels in children with sickle cell disease. J Pediatr Hematol Oncol 2002;24(5):374–379. DOI: 10.1097/00043426-200206000-00010Try link to: Google; Similars in: SciELO Network Articles in Google Scholar by Vinod V. Balasa, M.D.: http://www.ncbi.nlm.nih.gov/pubMed. Links: Medline, CrossRef.
Moher D, Liberati A, Tetzlaff J, et al. Preferred reporting items for systematic reviews and meta analysis; the PRISMA statement. BMJ 2009;339(jul21 1):b2535. DOI: 10.1136/bmj.b2535. https://www.bmj.com/content/339/bmj.b2535.
Houston PE, Rana S, Sekhsaria S, et al. Homocysteine in sickle cell disease: relationship to stroke. Am J Med 1997;103((3):192–196. DOI: 10.1016/S0002-9343(97)00129-0. https://www.sciencedirect.com/journal/the-american-journal-of-medicine.
Schnog JB, Van der Dijs FPL, Brouwer DAJ, et al. Comments from the editor-in-chief. J Pediat Hematol/Oncol 2000;22(2):184–185. DOI: 10.1097/00043426-200003000-00022.
Vander Jagt DJ, Shores J, Okorodudu A, et al. Hypocholesterolemia in Nigerian children with sickle cell disease. J Trop Pediat 2002;48(3):156–161. DOI: 10.1093/tropej/48.3.156. https://academic.oup.com/tropej/article/48/3/156/1617112.
van der Dijs FPL, Schnog JJB, Brouwer DAJ, et al. Elevated homocysteine levels indicate suboptimal folate status in pediatric sickle cell patients. Am J Hematol 1998;59(3):192–198. DOI: 10.1002/(SICI)1096-8652(199811)59:3<192::AID-AJH3>3.0.CO;2-8.
Balasa VV, Gruppo RA, Gartside PS, et al. Correlation of the C677T MTHFR genotype with homocysteine levels in children with sickle cell disease. J Pediatr Hematol Oncol 1999;21(5):397–400. DOI: 10.1097/00043426-199909000-00011. https://www.ncbi.nlm.nih.gov/pubmed/10524453.
Rodriguez-Cortes HM, Griener JC, Hyland K, et al. Plasma homocysteine levels and folate status in children with sickle cell anemia. J Pediatr Hematol Oncol 1999;3(3):219–223. DOI: https://onlinelibrary.wiley.com/doi/pdf/10.1002/ajh.20073.
Ajayi OI, Bwayo-Weaver S, Chirla S, et al. Cobalamin status in sickle cell disease. Int J Lab Hematol 2013;35(1):31–37. DOI: 10.1111/j.1751-553X.2012.01457.x. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3484229/.
Ali Z, Troncoso JC, Fowler DR. Recurrent cerebral venous thrombosis associated with heterozygote methylene tetrahydrofolate reductase C677T mutation and sickle cell trait without homocysteinemia: an autopsy case report and review of literature. Forensic Sci Int 2014;242:e52–e55. DOI: 10.1016/j.forsciint.2014.07.007. https://europepmc.org/abstract/med/25074331.
Vilas-Boas W, Veloso Cerqueira BA, Figueiredo CVB, et al. Association of homocysteine and inflammatory related molecules in sickle cell anemia. Hematology 2016;21(2):126–131. DOI: https://doi.org/10.1179/1607845415Y.0000000048ISSN: 1024-5332 (Print) 1607-8454.
Abdelsalam KEA. Evaluation of cardiac function tests in sudanese adult patients with sickle cell trait. Med J Indones 2016;25(3):151–156. DOI: 10.13181/mji.v25i3.1412. https://pdfs.semanticscholar.org/f7bd/0117319de65032a66ea2b08537a67e724a07.pdf.
Cattaneo M. Hyperhomocysteinemia and thrombosis. Lipids 2001;36(Suppl.):13–26. DOI: https://onlinelibrary.wiley.com/doi/abs/10.1007/s11745-001-0677-9.
Sadeghian S, Fallahi F, Salarifar M, et al. Homocysteine, vitamin B12 and folate levels in premature coronary artery disease. BMC Cardiovasc Disord 2006;6(1):38. DOI: 10.1186/1471-2261-6-38/PMID:17002799/PMCID:PMC1592513.
Virdis A, Ghiadoni L, Salvetti G, et al. Hyperhomocysteinemia: is a novel risk factor in hypertension? J Nephrol 2002;15:414–421. http://europepmc.org/abstract/med/12243373.
Johnkennedy N, Uche UB, Chidozie NJ, et al. Alterations of homocysteine in sickle cell anaemia. J Med Biol Sci Re 2015;1(4):44–46. http://oaji.net/articles/2015/2206-1437975476.pdf. ISSN: 2449-1810.
Ozdem S, Kupesiz A, Yesilipek A. Plasma homocysteine levels in patients with β‐thalassaemia major. Scandinav J Clin Laborat Investigat 2008;68(2):134–139. DOI: 10.1080/00365510701516343. https://www.ncbi.nlm.nih.gov/pubmed/18382931.
Al-Maktari LAS, Al-Nuzaily MAK, Bamashmoos SA, et al. Thrombotic events in patients with sickle cell anemia: relationship to protein C, S and total homocysteine levels. Int J Curr Aca Rev 2014;2(2):17–24. http://www.ijcrar.com/vol-2-2/Lutfi%20AS.%20Al-Maktari,%20et%20al.pdf. ISSN: 2347-3215.
Pandey S, Pandey HR, Mishra RM, et al. Increased homocysteine level in Indian sickle cell anemia patients. Ind J Clin Biochem 2012;27(1):103–104. DOI: 10.1007/s12291-011-0158-7. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3286591/.
Dhar M, Bellevue R, Brar S, et al. Mild hyperhomocysteinemia in adult patients with sickle cell disease: a common finding unrelated to folate and cbalamin status. Am J Hematol 2004;76(2):114–120. DOI: https://onlinelibrary.wiley.com/doi/abs/10.1002/ajh.20073/.