Relationship between MTHFR C677T gene polymorphism and oxidative stress levels in patients with H-type hypertension at high altitude
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摘要: 目的 分析高海拔地区Hcy及其代谢酶MTHFR C677T与氧化应激水平的关系。方法 随机选取玉树地区(海拔3 800~4 200 m)H型高血压患者30例(H型高血压组)、非H型高血压患者30例(非H型高血压组)和健康受试者30例(健康对照组),以及西宁地区(海拔2 260 m)H型高血压患者30例(H型高血压组)、非H型高血压患者30例(非H型高血压组)和健康受试者30例(健康对照组)。检测受试者血压、Hcy、氧化型谷胱甘肽(GSSG)、一氧化氮(NO)、超氧化物歧化酶(SOD)水平及亚甲基四氢叶酸还原酶(MTHFR C667T)基因型。结果 高Hcy水平患者具更高GSSG水平(P < 0.05);MTHFR C677T突变基因型患者具有更高的SOD、NO水平(TT型>CT型>CC型)(P < 0.05);Hcy与NO水平呈负相关性(r=-0.712,P < 0.01),SOD与C677T基因型突变呈正相关(r=0.707,P < 0.01),NO、Hcy与C677T基因型突变均呈正相关(r=0.642、0.452,P < 0.05)。高海拔地区人群具更高的氧化应激和Hcy水平,更低的C677T突变基因型频率。结论 Hcy水平和MTHFR C677T突变基因型与抗氧化水平呈正相关性。
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关键词:
- H型高血压 /
- MTHFR基因多态性 /
- 高海拔 /
- 氧化应激
Abstract: Objective To analyse the relationship between Hcy and its metabolic enzyme MTHFR C677T and the level of oxidative stress at high altitude.Methods In this study, 30 patients with H-type hypertension (H-type hypertension group), 30 patients with non-H-type hypertension (non-H-type hypertension group), and 30 healthy subjects (healthy control group) were randomly selected from Yushu area (3 800-4 200 m above sea level), and 30 patients with H-type hypertension(H-type hypertension group), 30 patients with non-H-type hypertension (non-H-type hypertension group), and 30 healthy subjects (healthy control group) were randomly selected from Xining area (2 260 m above sea level). Blood pressure, Hcy, oxidised glutathione (GSSG), nitric oxide (NO), superoxide dismutase (SOD) levels, and methylenetetrahydrofolate reductase (MTHFR C667T) genotype were measured.Results Patients with high Hcy levels exhibited higher GSSG levels (P < 0.05), patients with the MTHFR C677T mutant genotype had higher SOD and NO levels (TT type>CT type>CC type, P < 0.05). Hcy levels were negatively correlated with NO levels (r=-0.712, P < 0.01), SOD was positively correlated with the C677T genotype mutation (r=0.707, P < 0.01), and both NO and Hcy levels were positively correlated with the C677T genotype mutation (r=0.642, 0.452, P < 0.05). Populations in high-altitude regions exhibited higher oxidative stress and Hcy levels, along with a lower frequency of the C677T mutant genotype.Conclusion Hcy levels and MTHFR C677T mutant genotypes are positively correlated with antioxidant levels.-
Key words:
- H-type hypertension /
- MTHFR gene polymorphism /
- high altitude /
- oxidative stress
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表 1 6组受试者一般资料
Table 1. General data of participants in 6 groups
例(%), X±S 项目 中海拔地区 高海拔地区 健康对照组
(30例)非H型高血压组
(30例)H型高血压组
(30例)健康对照组
(30例)非H型高血压组
(30例)H型高血压组
(30例)年龄/岁 52.10±11.41 56.23±8.48 55.13±13.39 59.07±15.72 57.00±12.19 58.17±15.81 男性 13(43.33) 5(16.67) 11(36.67) 14(46.67) 10(33.33) 13(43.33) BMI/(kg/m2) 24.73±4.30 25.12±2.87 24.74±3.42 25.01±3.40 25.84±3.68 25.556±4.29 AST/(U/L) 24.50±5.61 23.00±5.90 24.23±5.82 24.30±10.99 22.13±4.45 24.90±8.77 ALT/(U/L) 24.88±9.26 27.23±8.83 26.20±10.10 30.17±9.19 26.13±8.64 23.80±9.70 Cr/(μmol/L) 64.33±14.76 66.63±9.31 66.83±15.59 72.07±13.25 65.67±17.41 72.53±12.59 GLU/(mmol/L) 4.97±0.54 4.52±0.69 4.65±0.33 4.91±0.83 4.67±0.79 4.70±0.89 UA/(μmol/L) 312.87±45.08 314.20±45.03 324.20±31.50 322.93±73.57 327.37±59.64 316.47±31.34 IMT左/mm 0.80±0.14 0.90±0.141) 0.91±0.182) 0.75±0.13 0.91±0.161)3) 1.00±0.191)2)3)4) IMT右/mm 0.84±0.15 0.87±0.13 0.90±0.17 0.80±0.12 0.87±0.13 1.05±0.151)2)3)4) LVMI/(g/m2) 71.46±21.94 73.27±18.19 82.59±25.48 75.74±17.673) 83.02±21.38 85.97±21.78 TC/(mmol/L) 3.66±0.83 4.02±0.50 4.08±0.97 4.24±1.013) 4.25±0.81 4.33±1.13 TG/(mmol/L) 0.99±0.33 1.26±0.28 1.47±0.341) 1.45±0.583) 1.62±0.56 2.09±0.971)2)4) HDL-C/(mmol/L) 1.12±0.28 1.09±0.20 0.95±0.1661)2) 1.05±0.32 0.93±0.231) 0.90±0.131) LDL-C/(mmol/L) 2.67±0.86 2.83±0.97 2.64±0.73 2.71±0.54 3.22±1.04 2.82±0.39 AST:门冬氨酸氨基转移酶;ALT:丙氨酸氨基转移酶;LDH:乳酸脱氢酶;BUN:尿素氮;Cr:肌酐;GLU:葡萄糖;UA:尿酸。与同海拔健康对照组比较,1)P < 0.05;与同海拔非H型高血压组比较,2)P < 0.05;与中海拔健康对照组比较,3)P < 0.05;与中海拔H型高血压组比较,4)P < 0.05。 表 2 6组受试者Hcy、氧化应激水平和血压比较
Table 2. Comparison of Hcy, oxidative stress level and blood pressure in 6 groups
X±S 项目 中海拔地区 高海拔地区 健康对照组
(30例)非H型高血压组
(30例)H型高血压组
(30例)健康对照组
(30例)非H型高血压组
(30例)H型高血压组
(30例)Hcy/(μmol/L) 7.39±1.27 8.29±1.94 13.46±2.401)2) 8.18±1.44 8.94±0.95 15.35±2.461)2)5) GSSG/(U/L) 0.79±0.37 5.05±2.461) 10.71±2.891)2) 1.18±0.27 7.06±2.591) 12.39±3.261)2) NO/(g/mol) 22.17±4.28 21.54±4.85 22.09±5.567 22.74±2.96 20.93±2.73 20.35±4.29 SOD/(ng/mL) 2.43±0.69 1.88±0.631) 1.86±0.561) 2.13±0.493) 1.23±0.461) 1.12±0.581)5) 收缩压/mmHg 121.87±7.49 162.80±9.821) 170.33±20.771) 124.57±5.82 162.83±16.641) 178.77±25.191)2) 舒张压/mmHg 79.60±3.41 96.87±6.651) 103.07±15.471)2) 84.10±1.32 106.63±9.481)4) 109.10±9.001) 与同海拔健康对照组比较,1)P < 0.05;与同海拔非H型高血压组比较,2)P < 0.05;与中海拔健康对照组比较,3)P < 0.05;与中海拔非H型高血压组比较,4)P < 0.05;与中海拔H型高血压组比较,5)P < 0.05。 表 3 两地区受试者基因型频率差异比较
Table 3. Comparison of genotype frequencies between the two regions
例(%) 基因型 中海拔地区 高海拔地区 χ2 P CC CT TT CC CT TT H型高血压组(30例) 8(26.67) 16(53.33) 6(20.00) 19(63.33) 8(26.67) 3(10.00) 8.148 0.017 非H型高血压组(30例) 6(20.00) 18(60.00) 6(20.00) 21(70.00) 8(26.67) 1(3.33) 15.751 < 0.001 健康对照组(30例) 7(23.33) 17(56.67) 6(20.00) 14(46.67) 10(33.33) 6(20.00) 4.148 0.126 表 4 两地区受试者不同基因型Hcy和氧化应激水平比较
Table 4. Comparison of Hcy and oxidative stress levels between different genotypes
例(%), X±S 组别 中海拔地区H型高血压组(30例) 高海拔地区H型高血压组(30例) 频率 Hcy/
(μmol/L)GSSG/
(U/L)NO/
(g/mol)SOD/
(ng/mL)频率 Hcy/
(μmol/L)GSSG/
(U/L)NO/
(g/mol)SOD/
(ng/mL)CC 8(26.67) 13.33±2.23 9.88±2.55 21.47±4.62 1.40±0.58 19(63.33) 13.90±0.90 12.74±3.35 18.22±3.96 1.07±0.64 CT 16(53.33) 13.07±2.39 11.08±3.17 23.04±5.58 1.81±0.22 8(26.67) 16.04±2.96 13.30±3.30 18.34±2.31 1.03±0.52 TT 6(20.00) 14.68±2.64 10.86±2.70 20.35±6.96 2.60±0.47 3(10.00) 16.54±2.63 11.24±3.11 24.50±2.70 1.25±0.570 F 1.005 0.456 0.561 16.100 4.381 1.011 12.667 0.369 P 0.379 0.639 0.577 < 0.001 0.023 0.377 <0.001 0.695 -
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