急性淋巴细胞白血病患儿认知功能障碍与MTHFR基因多态性的相关性

doi:10.3969/j.issn.2095-9400.2021.04.010

Abstract
Figure/Table
References (18)
Related Citation (15)

Download: PDF (1458 KB) HTML (1 KB)
Export: BibTeX | EndNote (RIS)

Abstract Objective: To investigate the relationship between methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms and plasma homocysteine (Hcy) and cognitive function in children with acute lymphoblastic leukemia (ALL). Methods: 39 children with acute lymphoblastic leukemia who were hospitalized in the Department of Hematology of the Second Affiliated Hospital & Yuying Children’s Hospital of Wenzhou Medical University from January 2015 to December 2019 were selected. Polymerase chain reaction-restriction enzyme fragment and length polymorphism analysis (PCR-RFLP) was used to detect the MTHFR genotype. The Wechsler Children’s Intelligence Scale Fourth Edition (WISC-IV) was used to assess cognitive function. Hcy level was also measured to analyze MTHFR. The correlation of gene polymorphism with Hcy level and cognitive function was analyzed by Pearson correlation. Results: Three genotypes existed in the C677T locus of the MTHFR gene in children with acute lymphoblastic leukemia. Compared with each genotype, Hcy level in the TT genotype was higher than that in the CT and CC types (P<0.05). There was a significant negative correlation between serum Hcy level and cognitive function, especially the operational IQ (PIQ) in children with ALL. MTHFR 677 C→T gene mutation was negatively correlated with ALL cognitive function (FIQ: r=-0.806, VIQ: r=-0.735, PIQ: r=-0.802, P<0.001). Conclusion: The MTHFR C677 T gene mutation, which may be a genetic susceptibility factor for cognitive impairment, can increase plasma Hcy levels and then affect cognitive function.

Key words： methylenetetrahydrofolate reductase gene polymorphism homocysteine cognitive function acute lymphoblastic leukemia

Received: 28 October 2020

	Service
	E-mail this article
	Add to my bookshelf
	Add to citation manager
	E-mail Alert
	RSS
	Articles by authors
	HUANG Zhen
	HU Linglong
	WANG Yao
	HUANG Tingting
	CHEN Min
	WANG Juxiang
	ZHOU Haixia
	LI Yuan.

URL:

https://xb.wmu.edu.cn/EN/10.3969/j.issn.2095-9400.2021.04.010 OR https://xb.wmu.edu.cn/EN/Y2021/V51/I4/307

参考文献：
[1] SMITH A D, REFSUM H, BOTTIGLIERI T, et al. Homocysteine and dementia: An international consensus statement[J]. J Alzheimers Dis, 2018, 62(2): 561-570.
[2] SONI R M, TIWARI S C, MAHDI A A,et al.Serum homocysteine and behavioral and psychological symptoms of dementia: Is there any correlation in Alzheimer's disease?[J]. Ann Neurosci, 2019, 25(3): 152-159.
[3] MOLL S,VARGA E A. Homocysteine and MTHFR mutations[J]. Circulation, 2015, 132(1): e6-9.
[4] RAI V. Association of C677T polymorphism (rs1801133) in MTHFR gene with depression[J]. Cell Mol Biol (Noisy-legrand), 2017, 63(6): 60-67.
[5] M A O X , H A N L . T h e r e l a t i o n s h i p o f Methylenetetrahydrofolate reductase gene C677T polymorphism and ischemic stroke in Chinese Han population[J]. Ann Clin Lab Sci, 2018, 48(2): 242-247.
[6] 中华医学会儿科学分会血液学组. 儿童急性淋巴细胞白血病诊疗建议(第四次修订)[J]. 中华儿科杂志, 2014, 52(9): 641-644.
[7] RICHARD A E, HODGES E K, HEINRICH K P. Visual attention and math performance in survivors of childhood acute lymphoblastic leukemia[J]. Arch Clin Neuropsychol, 2018, 33(8): 1015-1023.
[8] KESLER S R, OGG R, REDDICK W E, et al. Brain network connectivity and executive function in long-term survivors of childhood acute lymphoblastic leukemia[J]. Brain Connect, 2018, 8(6): 333-342.
[9] BOULET-CRAIG A, ROBAEY P, LANIEL J, et al. DIVERGT screening procedure predicts general cognitive functioning in adult long-term survivors of pediatric acute lymphoblastic leukemia: A PETALE study[J]. Pediatr Blood Cancer, 2018, 65(9): e27259.
[10] FELLAH S, CHEUNG Y T, SCOGGINS M A, et al. Brain activity associated with attention deficits following chemotherapy for childhood acute lymphoblastic leukemia [J]. J Natl Cancer Inst, 2019, 111(2): 201-209.
[11] 朱晓颖, 刘聪辉, 戈艳蕾. NO/ET-1 及HCY水平对重度OSAHS患者认知功能障碍的诊断效能[J]. 临床耳鼻咽喉头颈外科杂志, 2018, 32(22): 1691-1695.
[12] MORETTI R, CARUSO P. The controversial role of homocysteine in neurology: From labs to clinical practice[J]. Int J Mol Sci, 2019, 20(1): 231.
[13] MCCULLY K S. Homocysteine, infections, polyamines, oxidative metabolism, and the pathogenesis of dementia and atherosclerosis[J]. J Alzheimers Dis, 2016, 54(4): 1283- 1290.
[14] WANG X, CHEN W, FU X, et al. Correction to: Reversal of homocysteine-induced neurotoxicity in rat hippocampal neurons by astaxanthin: evidences for mitochondrial dysfunction and signaling crosstalk[J]. Cell Death Discov, 2019, 5: 70.
[15] LIU L, LIANG J, LIU Q, et al. Elevated plasma homocysteine levels in anti-N-methyl-D-aspartate receptor encephalitis[J]. Front Neurol, 2019, 10: 464.
[16] 韦玉鲁. 高同型半胱氨酸血症与脑血管疾病相关研究进展[J]. 医学理论与实践, 2019, 32(7): 968-969.
[17] LUPI-HERRERA E, SOTO-LÓPEZ M E, LUGO-DIMAS A J, et al. Polymorphisms C677T and A1298C of MTHFR gene: Homocysteine levels and prothrombotic biomarkers in coronary and pulmonary thromboembolic disease[J]. Clin Appl Thromb Hemost, 2019, 25: 1076029618780344.
[18] KAMDAR K Y, KRULL K R, EL-ZEIN R A, et al. Folate pathway polymorphisms predict deficits in attention and processing speed after childhood leukemia therapy[J]. Pediatr Blood Cancer, 2011, 57(3): 454-460.

[1]	. [J]. JOURNAL OF WEZHOU MEDICAL UNIVERSITY, 2022, 52(8): 675-677,681.