Association between MTHFR gene polymorphism and primary hypertension in children
WANG Hui, LIU Yan-Yan, ZHANG Yu, CHEN Xiao-Li, SHI Lin
Peking Union Medical College/Chinese Academy of Medical Sciences/Capital Institute of Pediatrics, Beijing 100020, China (Shi L, Email: shilin9789@126.com)
Abstract Objective To study the distribution characteristics of methylenetetrahydrofolate reductase (MTHFR) C677T gene polymorphism in children with primary hypertension, and to explore the association between MTHFR C677T gene polymorphism and H-type hypertension in children. Methods A total of 121 children with primary hypertension who were hospitalized in the department of cardiovascular medicine from January to July 2021, newly diagnosed, and untreated were retrospectively selected as the subjects. The children were divided into three groups: CC genotype (19 children), CT genotype (51 children), and TT genotype (51 children). According to the serum homocysteine (Hcy) level, they were divided two groups: H-type hypertension (47 children) and simple hypertension (74 children). The medical data were compared between the groups. The association between MTHFR C677T gene polymorphism and H-type hypertension was evaluated. Results The mutation frequency of T allele in children with primary hypertension was significantly higher than that in healthy adults in Beijing and Chinese Han adults (P<0.001). The serum Hcy level in the TT genotype group was significantly higher than that in the CC and CT genotype groups (P<0.001). The serum Hcy level in the H-type hypertension group was significantly higher than that in the simple hypertension group (P<0.001), and MTHFR C677T was mostly TT genotype, which was associated with the risk of H-type hypertension (OR=12.71, P<0.001). There was no significant difference in the incidence rate of target organ damage between the H-type hypertension and simple hypertension groups (P>0.05). However, multiple organ involvement was observed in the H-type hypertension group at diagnosis, accounting for 11% (5/47). Conclusions The mutation rate of MTHFR C677T T allele in children with primary hypertension is high and associated with the serum Hcy level. TT genotype is an independent risk factor for H-type hypertension in children, and it may be related to the severity of early target organ damage. Citation:Chinese Journal of Contemporary Pediatrics, 2022, 24(5): 579-584
Qian X, Lu Z, Tan M, et al. A meta-analysis of association between C677T polymorphism in the methylenetetrahydrofolate reductase gene and hypertension[J]. Eur J Hum Genet, 2007, 15(12): 1239-1245. PMID: 17726486. DOI: 10.1038/sj.ejhg.5201914.
Song J, Hou J, Zhao Q, et al. Polymorphism of MTHFR C677T gene and the associations with the severity of essential hypertension in northern Chinese population[J]. Int J Hypertens, 2020, 2020: 1878917. PMID: 33145104. PMCID: PMC7596525. DOI: 10.1155/2020/1878917.
Yang B, Fan S, Zhi X, et al. Geographical and ethnic distribution of MTHFR gene polymorphisms and their associations with diseases among Chinese population[J]. Clin Genet, 2017, 92(3): 243-258. PMID: 27888505. DOI: 10.1111/cge.12929.
Qian XL, Cao H, Zhang J, et al. The prevalence, relative risk factors and MTHFR C677T genotype of H type hypertension of the elderly hypertensives in Shanghai, China: a cross-section study: prevalence of H type hypertension[J]. BMC Cardiovasc Disord, 2021, 21(1): 376. PMID: 34348647. PMCID: PMC8336333. DOI: 10.1186/s12872-021-02151-x.
12 ALFRED. ALFRED allele frequency in tabular format[EB/OL]. [2021-08-20]. https://alfred.med.yale.edu/alfred/SiteTable1A_working.asp?siteuid=SI001032G.
Kumawat R, Gowda SH, Debnath E, et al. Association of single nucleotide polymorphisms (SNPs) in genes encoding for folate metabolising enzymes with glioma and meningioma in Indian population[J]. Asian Pac J Cancer Prev, 2018, 19(12): 3415-3425. PMID: 30583664. PMCID: PMC6428555. DOI: 10.31557/APJCP.2018.19.12.3415.
Cheng J, Tao F, Liu Y, et al. Associations of methylenetetrahydrofolate reductase C677T genotype with blood pressure levels in Chinese population with essential hypertension[J]. Clin Exp Hypertens, 2018, 40(3): 207-212. PMID: 29436860. DOI: 10.1080/10641963.2017.1281937.
Yadav S, Longkumer I, Joshi S, et al. Methylenetetrahydrofolate reductase gene polymorphism, global DNA methylation and blood pressure: a population based study from North India[J]. BMC Med Genomics, 2021, 14(1): 59. PMID: 33639933. PMCID: PMC7912464. DOI: 10.1186/s12920-021-00895-1.
Tang Z, Xiao L, Wang JQ, et al. Analysis of metabolism-related indicators and MTHFR gene polymorphism in patients with H-type hypertension[J]. Minerva Med, 2017, 108(2): 103-107. PMID: 27973469. DOI: 10.23736/S0026-4806.16.04951-X.
Huang LQ, Wu CX, Wei HQ, et al. Clinical characteristics of H-type hypertension and its relationship with the MTHFR C677T polymorphism in a Zhuang population from Guangxi, China[J]. J Clin Lab Anal, 2020, 34(11): e23499. PMID: 32790014. PMCID: PMC7676193. DOI: 10.1002/jcla.23499.
