目的 分析原发性高血压儿童亚甲基四氢叶酸还原酶（methylenetetrahydrofolate reductase，MTHFR）基因C677T多态性分布特征，探讨其与儿童H型高血压的相关性。 方法 回顾性选取2021年1~7月于心血管内科住院、初次诊断未经治疗的121例原发性高血压儿童为研究对象，按基因型分为CC型组（19例）、CT型组（51例）和TT型组（51例）；按血清同型半胱氨酸（homocysteine，Hcy）水平分为H型高血压组（47例）和单纯高血压组（74例），比较各组间临床资料差异，分析MTHFR基因C677T多态性与儿童H型高血压的相关性。 结果 原发性高血压儿童T等位基因突变频率高于北京地区健康成年人群和中国汉族成年人群（P<0.001）。TT型组血清Hcy水平高于CC型组和CT型组（P<0.001）。H型高血压组血清Hcy水平高于单纯高血压组（P<0.001），且MTHFR基因C677T多为TT基因型，TT基因型与H型高血压的发生风险存在关联（OR=12.71，P<0.001）。H型高血压组和单纯高血压组间靶器官损伤发生率差异无统计学意义（P>0.05），但初次诊断时，H型高血压组即可存在多脏器受累情况，占11%（5/47）。 结论 原发性高血压儿童MTHFR基因C677T的T等位基因突变率高且与血清Hcy水平具有一定关联，TT基因型是儿童H型高血压的独立危险因素，与早期靶器官损伤严重程度可能相关。 引用格式：中国当代儿科杂志，2022，24（5）：579-584
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
关键词
原发性高血压 /
亚甲基四氢叶酸还原酶 /
高同型半胱氨酸血症 /
基因多态性 /
儿童
Key words
Primary hypertension /
Methylenetetrahydrofolate reductase /
Hyperhomocysteinemia /
Gene polymorphism /
Child
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参考文献
1 Sabri M, Gheissari A, Mansourian M, et al. Essential hypertension in children, a growing worldwide problem[J]. J Res Med Sci, 2019, 24: 109. PMID: 31949460. PMCID: PMC6950331. DOI: 10.4103/jrms.JRMS_641_19.
2 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.
3 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.
4 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.
5 中国高血压防治指南修订委员会, 高血压联盟(中国, 中华医学会心血管病学分会中国医师协会高血压专业委员会, 等. 中国高血压防治指南(2018年修订版)[J]. 中国心血管杂志, 2019, 24(1): 24-56. DOI: 10.3969/j.issn.1007-5410.2019.01.002.
6 刘杨, 石琳, 林瑶, 等. 原发性高血压患儿血压变异性与靶器官损伤的关系研究[J]. 中华儿科杂志, 2019, 57(2): 93-97. PMID: 30695881. DOI: 10.3760/cma.j.issn.0578-1310.2019.02.006.
7 孙宁玲, 李建平, 卢新政, 等. H型高血压诊断标准依据解读[J]. 中华高血压杂志, 2017, 25(6): 508-510. DOI: 10.16439/j.cnki.1673-7245.2017.06.004.
8 李丹丹, 叶阿里, 甘勇, 等. 北京地区汉族人群MTHFR C677T基因多态性分析[J]. 临床检验杂志, 2019, 37(2): 156-160. DOI: 10.13602/j.cnki.jcls.2019.02.19.
9 Yang B, Liu Y, Li Y, et al. Geographical distribution of MTHFR C677T, A1298C and MTRR A66G gene polymorphisms in China: findings from 15357 adults of Han nationality[J]. PLoS One, 2013, 8(3): e57917. PMID: 23472119. PMCID: PMC3589470. DOI: 10.1371/journal.pone.0057917.
10 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.
11 江载芳, 申昆玲, 沈颖. 诸福棠实用儿科学[M]. 8版. 北京: 人民卫生出版社, 2015: 581-583.
12 ALFRED. ALFRED allele frequency in tabular format[EB/OL]. [2021-08-20]. https://alfred.med.yale.edu/alfred/SiteTable1A_working.asp?siteuid=SI001032G.
13 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.
14 高晓峰, 赵俊琴, 周青, 等. 高血压病人MTHFR C677T基因多态性与血浆同型半胱氨酸水平的关系探讨[J]. 中西医结合心脑血管病杂志, 2020, 18(24): 4207-4209. DOI: 10.12102/j.issn.1672-1349.2020.24.024.
15 Ostrakhovitch EA, Tabibzadeh S. Homocysteine and age-associated disorders[J]. Ageing Res Rev, 2019, 49: 144-164. PMID: 30391754. DOI: 10.1016/j.arr.2018.10.010.
16 Li T, Yu B, Liu Z, et al. Homocysteine directly interacts and activates the angiotensin II type I receptor to aggravate vascular injury[J]. Nat Commun, 2018, 9(1): 11. PMID: 29296021. PMCID: PMC5750214. DOI: 10.1038/s41467-017-02401-7.
17 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.
18 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.
19 向海卿, 黄小丽, 侯强波, 等. 连南瑶族人群H型高血压与亚甲基四氢叶酸还原酶基因C677T多态性的关系[J]. 中华高血压杂志, 2020, 28(8): 767-770. DOI: 10.16439/j.cnki.1673-7245.2020.08.019.
20 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.
21 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.
22 刘岩岩, 林瑶, 刘杨, 等. 儿童H型高血压血压变异性研究[J]. 中华实用儿科临床杂志, 2021, 36(13): 995-998. DOI: 10.3760/cma.j.cn101070-20200214-00150.
基金
北京市医院管理中心儿科学科协同发展中心儿科专项（XTYB201801）。
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