Markan Suchita, Sachdeva Meenakshi, Sehrawat Badan Singh, Kumari Savita, Jain Sanjay, Khullar Madhu
Department of Experimental Medicine and Biotechnology, Post Graduate Institute of Medical Education and Research, Laboratory no. 2033, Research block B, Chandigarh 160012, India.
Mol Cell Biochem. 2007 Aug;302(1-2):125-31. doi: 10.1007/s11010-007-9434-5. Epub 2007 Mar 1.
The goals of our present study were to measure plasma homocysteine levels and determine their association with methylenetetrahydrofolate reductase (MTHFR) gene polymorphisms (C677T and A1298C) in essential hypertensive subjects. Plasma total homocysteine and folic acid levels were measured in essential hypertensive patients (n = 153) before and after oral supplementation with either 5 mg folic acid tablet/day or 5 mg placebo/day for 4 weeks and compared with age and sex matched normotensive controls (n = 133). MTHFR gene polymorphisms (C677T and A1298C) were studied by restriction fragment length polymorphism and correlated with plasma homocysteine levels. Homocysteine levels were significantly higher in hypertensive patients as compared to controls and showed a negative correlation with plasma folate levels. Folic acid supplementation (5 mg/day) for 4 weeks resulted in a significant decrease in plasma homocysteine concentrations in these patients. Patients carrying MTHFR 677T allele (OR = 1.90; 95%CI: 1.14-3.19) or MTHFR 1298C (OR = 2.6, 95%CI: 1.55-4.40) allele were at increased risk of hypertension. The frequency of co-occurrence of MTHFR 677 CT/1298 CC genotypes was significantly higher in the patients compared to controls (P < 0.05) and was associated with increased risk of hypertension (OR = 3.54, 95%CI: 0.37-4.30). Subjects with MTHFR 1298 CC genotype had significantly higher homocysteine levels compared to those with MTHFR 1298 AA genotype (P < 0.05). Our results indicate that MTHFR 677T and 1298C alleles and co-occurrence of MTHFR 677 CT/MTHFR 1298 CC genotypes are associated with increased risk of hypertension and MTHFR 1298 CC genotype is associated with higher homocysteine levels in our subjects.
我们当前研究的目的是测量原发性高血压患者的血浆同型半胱氨酸水平，并确定其与亚甲基四氢叶酸还原酶（MTHFR）基因多态性（C677T和A1298C）之间的关联。对153例原发性高血压患者口服5毫克叶酸片/天或5毫克安慰剂/天，持续4周，测量服药前后的血浆总同型半胱氨酸和叶酸水平，并与年龄和性别匹配的血压正常对照组（133例）进行比较。通过限制性片段长度多态性研究MTHFR基因多态性（C677T和A1298C），并将其与血浆同型半胱氨酸水平进行关联分析。与对照组相比，高血压患者的同型半胱氨酸水平显著更高，且与血浆叶酸水平呈负相关。对这些患者补充叶酸（5毫克/天）4周后，血浆同型半胱氨酸浓度显著降低。携带MTHFR 677T等位基因（OR = 1.90；95%CI：1.14 - 3.19）或MTHFR 1298C等位基因（OR = 2.6，95%CI：1.55 - 4.40）的患者患高血压的风险增加。与对照组相比，患者中MTHFR 677 CT/1298 CC基因型的共现频率显著更高（P < 0.05），且与高血压风险增加相关（OR = 3.54，95%CI：0.37 - 4.30）。与MTHFR 1298 AA基因型的受试者相比，MTHFR 1298 CC基因型的受试者同型半胱氨酸水平显著更高（P < 0.05）。我们的结果表明，MTHFR 677T和1298C等位基因以及MTHFR 677 CT/MTHFR 1298 CC基因型的共现与高血压风险增加相关，且MTHFR 1298 CC基因型与我们研究对象中更高的同型半胱氨酸水平相关。
