中国高血压人群中叶酸、同型半胱氨酸与MTHFR、MTR和MTRR基因多态性与血脂异常的联合关联：一项横断面研究
Joint associations of folate, homocysteine and MTHFR, MTR and MTRR gene polymorphisms with dyslipidemia in a Chinese hypertensive population: a cross-sectional study.
作者信息
Li Wen-Xing, Lv Wen-Wen, Dai Shao-Xing, Pan Ming-Luo, Huang Jing-Fei
机构信息
Institute of Health Sciences, Anhui University, Hefei, 230601, PR China.
State Key Laboratory of Genetic Resources and Evolution, Kunming Institute of Zoology, Chinese Academy of Sciences, Kunming, 650223, PR China.
出版信息
Lipids Health Dis. 2015 Sep 4;14:101. doi: 10.1186/s12944-015-0099-x.
BACKGROUND
Dyslipidemia is a well-established risk factor for cardiovascular disease. Serum lipids were affected by several gene polymorphisms, folate, homocysteine and other metabolite levels. We aim to investigate the effects of homocysteine metabolism enzyme polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) and their interactions with folate, homocysteine on serum lipid levels in Chinese patients with hypertension.
METHODS
Participants were 480 hypertensive adults that enrolled in September to December 2005 from six different Chinese hospitals (Harbin, Shanghai, Shenyang, Beijing, Xi'an, and Nanjing). Known MTHFR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G genotypes were determined by PCR-RFLP methods. Serum folate was measured by chemiluminescent immunoassay, homocysteine was measured by high-performance liquid chromatography, serum lipids parameters were determined by an automatic biochemistry analyzer, low-density lipoprotein was calculated by Friedewald's equation. Unitary linear regression model was used to assess the associations of gene polymorphisms, folate and homocysteine on serum lipid profiles. Unconditional logistic regression model was applied to test the interactions of folate, homocysteine and gene polymorphisms on dyslipidemia.
RESULTS
No correlations between gene polymorphisms and homocysteine on serum lipid profiles. Compared with normal folate patients, patients with low folate showed higher odds of hypertriglyceridemia (OR = 2.02, 95 % CI: 1.25-3.25, P = 0.004) and low levels of high-density lipoprotein cholesterol (OR = 1.88, 95 % CI: 1.07-3.28, P = 0.027). Each of four gene polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) combined with low folate showed higher odds of hypertriglyceridemia (P for trend: 0.049, 0.004, 0.007 and 0.005, respectively). MTHFR C677T and A1298C with low folate showed higher odds of low levels of high-density lipoprotein cholesterol (P for trend: 0.008 and 0.031).
CONCLUSIONS
Low folate status and homocysteine metabolism gene polymorphisms (MTHTR C677T, MTHFR A1298C, MTR A2756G and MTRR A66G) may have a synergistic effect increased the incidence of dyslipidemia in Chinese hypertensive population.
背景
血脂异常是心血管疾病公认的危险因素。血清脂质受多种基因多态性、叶酸、同型半胱氨酸及其他代谢物水平的影响。我们旨在研究同型半胱氨酸代谢酶基因多态性（MTHTR C677T、MTHFR A1298C、MTR A2756G和MTRR A66G）及其与叶酸、同型半胱氨酸的相互作用对中国高血压患者血清脂质水平的影响。
方法
研究对象为2005年9月至12月从中国六家不同医院（哈尔滨、上海、沈阳、北京、西安和南京）招募的480例高血压成年人。采用聚合酶链反应-限制性片段长度多态性（PCR-RFLP）方法测定已知的MTHFR C677T、MTHFR A1298C、MTR A2756G和MTRR A66G基因型。采用化学发光免疫分析法测定血清叶酸，采用高效液相色谱法测定同型半胱氨酸，采用自动生化分析仪测定血清脂质参数，采用Friedewald公式计算低密度脂蛋白。采用单因素线性回归模型评估基因多态性、叶酸和同型半胱氨酸与血清脂质谱的相关性。采用非条件逻辑回归模型检验叶酸、同型半胱氨酸和基因多态性对血脂异常的相互作用。
结果
基因多态性与同型半胱氨酸与血清脂质谱之间无相关性。与叶酸正常的患者相比，叶酸水平低的患者高甘油三酯血症的发生率更高（OR = 2.02，95%CI：1.25 - 3.25，P = 0.004），高密度脂蛋白胆固醇水平更低（OR = 1.88，95%CI：1.07 - 3.28，P = 0.027）。四种基因多态性（MTHTR C677T、MTHFR A1298C、MTR A2756G和MTRR A66G）中的每一种与低叶酸联合时，高甘油三酯血症的发生率更高（趋势P值分别为：0.049、0.004、0.007和0.005）。MTHFR C677T和A1298C与低叶酸联合时，高密度脂蛋白胆固醇水平低的发生率更高（趋势P值分别为：0.008和0.031）。
结论
低叶酸状态和同型半胱氨酸代谢基因多态性（MTHTR C677T、MTHFR A1298C、MTR A2756G和MTRR A66G）可能具有协同作用，增加中国高血压人群血脂异常的发生率。
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