All issues > Volume 47(10); 2004

Original Article

Korean J Pediatr. 2004;47(10):1053-1057. Published online October 15, 2004.

Methylenetetrahydrofolate Reductase C677T and A1298C Polymorphisms and Risk of Down Syndrome

Kyu Young KY Chae¹, Jin Hee JH Han², Ji Yeong JY Seo¹, Min Jung MJ Cho¹, Sehyun SH Kim³, Nam Keun NK Kim²

¹Department of Pediatrics, College of Medicine, Pochon CHA University, Seongnam, Korea
²Department of Institute for Clinical Research, College of Medicine, Pochon CHA University, Seongnam, Korea
³Department of Preventive Medicine, College of Medicine, Pochon CHA University, Seongnam, Korea

Correspondence Nam Keun NK Kim ,Email: nkkim@cha.ac.kr

Abstract

Purpose
: The C677T polymorphism of the methylenetetrahydrofolate reductase(MTHFR) has been suggested as a risk factor of maternal meiotic nondisjunction for Down syndrome. Recently, a second genetic polymorphism in MTHFR at position 1298 was reported. However, a positive association between the A1298C MTHFR polymorphism and Down syndrome has not been reported. Therefore, this study was undertaken to determine which polymorphism of MTHFR gene was associated with the increased risk of a child suffering from Down syndrome(DS).
Methods
: We enrolled 33 patients with Down syndrome and 100 healthy individuals and analyzed the MTHFR C677T and A1298C polymorphism by a PCR-restriction fragment length assay.
Results
: Frequencies of MTHFR C677T genotypes(CC, CT, and TT) were 9(27%), 22(67%), and 2 (6%) in the DS patients and 24(24%), 55(55%) and 21(21%) in the control, respectively. The frequency of mutant 677TT was significantly low in the DS patients(OR : 0.14; 95% CI : 0.02-0.95; P= 0.04). For the MTHFR A1298C polymorphism, frequencies of genotypes(AA, AC, and CC) were 16(48 %), 15(45%) and 1(3%) in DS patients and 77(77%), 21(21%) and 2(2%) in the control, respectively. The frequency of mutant 1298AC was significantly increased in DS patients with an odds ratio of 3.3(95% CI : 1.39-7.82; P=0.007).
Conclusion
: Our results suggest that MTHFR mutant 677TT may have a protective effect against Down syndrome, but MTHFR mutant 1298AC may be an independent risk factor in Down syndrome.

Keywords :Down syndrome, MTHFR, Polymorphism