ORIGINAL ARTICLE   

Minerva Medica 2021 April;112(2):261-8

DOI: 10.23736/S0026-4806.20.06462-9

Copyright © 2020 EDIZIONI MINERVA MEDICA

language: English

Relationship between cobalt transporter II gene rs9606756 site mutant and serum homocysteine level and recurrent cerebral infarction in young and middle-aged people

Jing LIU ¹, Yan JIANG ¹, Deshui LIU ², Hao ZHANG ², Tuantuan CHEN ¹, Guangping ZHANG ¹, Hongbin LIU ¹, Shu DU ¹, Zaihong LIN ¹, Yan JIN ¹, Xiaohua LI ¹ ✉

¹ Department of Neurology, The Third Affiliated Hospital of Qiqihar Medical University, Qiqihar, China; ² Institute of Medical Sciences, Qiqihar Medical University, Qiqihar, China

BACKGROUND: This study aimed to investigate the effect of cobalt transporter II gene (rs1801198, rs2301957, rs9606756) polymorphism on serum homocysteine level and its correlation with young and middle recurrent cerebral infarction.
METHODS: A total of 348 young and middle-aged patients with cerebral infarction admitted to The Third Affiliated Hospital of Qiqihar Medical University from January 2017 to March 2018 were enrolled. The patients were divided into recurrent and non-recurrent groups according to follow-up. DNA was extracted from the peripheral blood of patients, and the DNA samples were genotyped by IlluminaBeadArray technology to detect the gene polymorphisms of cobalt transporter II (TCN2) sites (rs1801198, rs2301957, rs9606756), and the homocysteine (hcy) level was determined by cyclic enzymatic method. VitB12 and folate levels were measured by chemiluminescence immunoassay, and holo transcobalamin (holoTC) expression levels were detected by enzyme-linked immunosorbent assay.
RESULTS: The frequency of alleles of rs9606756 mutation in the recurrent group was higher than that in the non-recurrent group (P<0.05), and the Hcy level in rs9606756 locus genotype AG+GG was significantly higher than the AA genotype in the recurrent group (P=0.031). Pearson correlation analysis showed that Hcy levels were associated with different genotypes of rs9606756 in the recurrent group (r=0.483, P=0.0003). The rs9606756 allele AA in SH-SY5Y cells was replaced with GG by point mutation experiment. The Hcy metabolism levels of wild and mutant cells were detected. The accumulation level of Hcy in the mutant group was significantly increased (P=0.007). The holoTC in the supernatant was significantly reduced in the mutant (P=0.032).
CONCLUSIONS: The TCN2 gene rs9606756 mutation is closely related to the level of Hcy metabolism in young and middle-aged patients, which may affect the recurrence of cerebral infarction. It is of great significance to further understand the pathogenesis, prevention and treatment of recurrent cerebral infarction in young and middle-aged patients.

KEY WORDS: Cobalt; Cerebral infarction; Homocysteine