Clinical and Experimental Pediatrics

The Korean Pediatric Society (대한소아청소년과학회)
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Polymorphisms of methylenetetrahydrofolate reductase are not a risk factor for Kawasaki disease in the Korean population

  • Yoon, Kyung-Lim (Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine) ;
  • Ko, Jin-Hee (Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine) ;
  • Shim, Kye-Shik (Department of Pediatrics, Kyung Hee University Hospital at Gangdong, Kyung Hee University School of Medicine) ;
  • Han, Mi-Young (Department of Pediatrics, Kyung-Hee University Medical Center, Kyung Hee University School of Medicine) ;
  • Cha, Sung-Ho (Department of Pediatrics, Kyung-Hee University Medical Center, Kyung Hee University School of Medicine) ;
  • Kim, Su-Kang (Department of Clinical Pharmacology, Kyung Hee University School of Medicine) ;
  • Jung, Joo-Ho (Department of Clinical Pharmacology, Kyung Hee University School of Medicine)
  • Received : 2011.02.23
  • Accepted : 2011.07.21
  • Published : 2011.08.15
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Abstract

Purpose: Hyperhomocysteinemia is known as a risk factor for atherosclerosis. Preclinical arteriosclerosis is noted and premature atherosclerosis is known to be accelerated in Kawasaki disease (KD) patients. Genetic polymorphisms in the 5,10-methylenetetrahydrofolate reductase (MTHFR) gene result in elevated plasma homocysteine concentrations and are known to be associated with the development of coronary artery disease. Our hypothesis is that single nucleotide polymorphisms (SNPs) of the MTHFR gene are related to the development of KD and coronary artery lesions (CALs). Methods: For this study, we selected 3 candidate single nucleotide polymorphisms (SNPs) (rs2274976, rs1801131, and rs1801133) of MTHFR. These SNPs are located on chromosome 1p36.3. We included 101 KD patients and 306 healthy adults as controls in this study. CALs were seen in 38 patients. Genotypes of the selected SNPs were determined by direct sequencing and analyzed with SNPAlyze. Results: The genetic distribution and allelic frequency of the 3 MTHFR SNPs (rs2274976, rs1801131, and rs1801133) were not significantly different in patients with KD compared to the control group (P=0.71, 0.17, and 0.96, respectively). There was no difference in the genetic distribution of the MTHFR SNPs between the normal control group and the CAL group (P=0.43, 0.39, 0.52 respectively). Conclusion: The genetic distribution of the MTHFR SNPs (rs2274976, rs1801131, and rs1801133) was not different in the KD group compared to the control group. In addition, the genetic distribution of these SNPs was not different in the CAL group compared to the control group in the Korean population.

Keywords

References

  1. Dajani AS, Taubert KA, Gerber MA, Shulman ST, Ferrieri P, Freed M, et al. Committee on Rheumatic Fever, Endocarditis, and Kawasaki Disease, Council on Cardiovascular Disease in the Young, American Heart Association. Diagnosis and therapy of Kawasaki disease in children. Circulation 1993;87:1776-80. https://doi.org/10.1161/01.CIR.87.5.1776
  2. Rowley AH, Shulman ST. Kawasaki syndrome. Pediatr Clin North Am 1999;46:313-29. https://doi.org/10.1016/S0031-3955(05)70120-6
  3. Clarke R, Daly L, Robinson K, Naughten E, Cahalane S, Fowler B, et al. Hyperhomocysteinemia: an independent risk factor for vascular disease. N Engl J Med 1991;324:1149-55. https://doi.org/10.1056/NEJM199104253241701
  4. Hankey GJ, Eikelboom JW. Homocysteine and vascular disease. Lancet 1999;354:407-13. https://doi.org/10.1016/S0140-6736(98)11058-9
  5. Hofmann MA, Lalla E, Lu Y, Gleason MR, Wolf BM, Tanji N, et al. Hyperhomocysteinemia enhances vascular inflammation and accelerates atherosclerosis in a murine model. J Clin Invest 2001;107:675-83. https://doi.org/10.1172/JCI10588
  6. Kawashiri M, Kajinami K, Nohara A, Yagi K, Inazu A, Koizumi J, et al. Plasma homocysteine level and development of coronary artery disease. Coron Artery Dis 1999;10:443-7. https://doi.org/10.1097/00019501-199910000-00002
  7. Sadeghian S, Fallahi F, Salarifar M, Davoodi G, Mahmoodian M, Fallah N, et al. Homocysteine, vitamin B12 and folate levels in premature coronary artery disease. BMC Cardiovasc Disord 2006;6:38. https://doi.org/10.1186/1471-2261-6-38
  8. Noto N, Okada T, Karasawa K, Ayusawa M, Sumitomo N, Harada K, et al. Age-related acceleration of endothelial dysfunction and subclinical atherosclerosis in subjects with coronary artery lesions after Kawasaki disease. Pediatr Cardiol 2009;30:262-8.
  9. Ghelani SJ, Singh S, Manojkumar R. Endothelial dysfunction in a cohort of North Indian children with Kawasaki disease without overt coronary artery involvement. J Cardiol 2009;53:226-31. https://doi.org/10.1016/j.jjcc.2008.11.006
  10. Takahashi M. The endothelium in Kawasaki disease: the next frontier. J Pediatr 1998;133:177-9. https://doi.org/10.1016/S0022-3476(98)70216-1
  11. Morita H, Taguchi J, Kurihara H, Kitaoka M, Kaneda H, Kurihara Y, et al. Genetic polymorphism of 5, 10-methylenetetrahydrofolate reductase (MTHFR) as a risk factor for coronary artery disease. Circulation 1997; 95:2032-6. https://doi.org/10.1161/01.CIR.95.8.2032
  12. Pinto X, Vilaseca MA, Garcia-Giralt N, Ferrer I, Palá M, Meco JF, et al. Homocysteine and the MTHFR 677C$\rightarrow$T allele in premature coonary artery disease. Case control and family studies. Eur J Clin Invest 2001;31:24-30. https://doi.org/10.1046/j.1365-2362.2001.00760.x
  13. Tsukahara H, Hiraoka M, Saito M, Nishida K, Kobata R, Tsuchida S, et al. Methylenetetrahydrofolate reductase polymorphism in Kawasaki disease. Pediatr Int 2000;42:236-40. https://doi.org/10.1046/j.1442-200x.2000.01229.x
  14. Kluijtmans LA, van den Heuvel LP, Boers GH, Frosst P, Stevens EM, van Oost BA, et al. Molecular genetic analysis in mild hyperhomocysteinemia: a common mutation in the methylenetetrahydrofolate reductase gene is a genetic risk factor for cardiovascular disease. Am J Hum Genet 1996; 58:35-41.
  15. Klerk M, Verhoef P, Clarke R, Blom HJ, Kok FJ, Schouten EG; MTHFR Studies Collaboration Group. MTHFR 677C$\rightarrow$T polymorphism and risk of coronary heart disease: a meta-analysis. JAMA 2002;288:2023-31. https://doi.org/10.1001/jama.288.16.2023
  16. van Bockxmeer FM, Mamotte CD, Vasikaran SD, Taylor RR. Methylenetetrahydrofolate reductase gene and coronary artery disease. Circulation 1997;95:21-3. https://doi.org/10.1161/01.CIR.95.1.21
  17. Schwartz SM, Siscovick DS, Malinow MR, Rosendaal FR, Beverly RK, Hess DL, et al. Myocardial infarction in young women in relation to plasma total homocysteine, folate, and a common variant in the methylenetetrahydrofolate reductase gene. Circulation 1997;96:412-7. https://doi.org/10.1161/01.CIR.96.2.412
  18. Martin YN, Salavaggione OE, Eckloff BW, Wieben ED, Schaid DJ, Weinshilboum RM. Human methylenetetrahydrofolate reductase pharmacogenomics: gene resequencing and functional genomics. Pharmacogenet Genomics 2006;16:265-77 https://doi.org/10.1097/01.fpc.0000194423.20393.08
  19. Allen NC, Bagade S, McQueen MB, Ioannidis JP, Kavvoura FK, Khoury MJ, et al. Systematic meta-analyses and field synopsis of genetic association studies in schizophrenia: the SzGene database. Nat Genet 2008;40: 827-34. https://doi.org/10.1038/ng.171
  20. Palomino-Morales R, Gonzalez-Juanatey C, Vazquez-Rodriguez TR, Rodriguez L, Miranda-Filloy JA, Fernandez-Gutierrez B, et al. A1298C polymorphism in the MTHFR gene predisposes to cardiovascular risk in rheumatoid arthritis. Arthritis Res Ther 2010;12:R71. https://doi.org/10.1186/ar2989

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