Ramachandran Vasudevan, Ismail Patimah, Stanslas Johnson, Shamsudin Norashikin
Genetic Research Group, Department of Biomedical Science, Faculty of Medicine and Health Sciences, Universiti Putra Malaysia, Selangor, Malaysia.
Cardiovasc Diabetol. 2009 Feb 25;8:11. doi: 10.1186/1475-2840-8-11.
The renin-angiotensin aldosterone system (RAAS) plays an important role in regulating the blood pressure and the genetic polymorphisms of RAAS genes has been extensively studied in relation to the cardiovascular diseases in various populations with conflicting results. The aim of this study was to determine the association of five genetic polymorphisms (A6G and A20C of angiotensinogen (AGT), MboI of renin, Gly460Trp of aldosterone synthase and Lys173Arg of adducin) of RAAS genes in Malaysian essential hypertensive and type 2 diabetic subjects.
RAAS gene polymorphisms were determined using mutagenically separated PCR and PCR-RFLP method in a total of 270 subjects consisting of 70 hypertensive subjects without type 2 diabetes mellitus (T2DM), 60 T2DM, 65 hypertensive subjects with T2DM and 75 control subjects.
There was significant difference found in age, body mass index, systolic/diastolic blood pressure, fasting plasma glucose and high density lipoprotein cholesterol levels between the hypertensive subjects with or without T2DM and control subjects. No statistically significant differences between groups were found in the allele frequency and genotype distribution for A20C variant of AGT gene, MboI of renin, Gly460Trp of aldosterone and Lys173Arg of adducin (p > 0.05). However, the results for A6G of AGT gene revealed significant differences in allele and genotype frequencies in essential hypertension with or without T2DM (p < 0.001).
Among the five polymorphisms of RAAS genes only A6G variant of AGT gene was significantly associated in Malaysian essential hypertensive and type 2 diabetic subjects. Therefore, A6G polymorphism of the AGT gene could be a potential genetic marker for increased susceptibility to essential hypertension with or without T2DMin Malaysian subjects.
肾素-血管紧张素-醛固酮系统(RAAS)在血压调节中起重要作用,并且RAAS基因的遗传多态性已在不同人群中针对心血管疾病进行了广泛研究,但结果相互矛盾。本研究的目的是确定RAAS基因的五个遗传多态性(血管紧张素原(AGT)的A6G和A20C、肾素的MboI、醛固酮合酶的Gly460Trp和内收蛋白的Lys173Arg)在马来西亚原发性高血压和2型糖尿病患者中的相关性。
采用诱变分离PCR和PCR-RFLP方法,对总共270名受试者进行RAAS基因多态性检测,其中包括70名无2型糖尿病(T2DM)的高血压患者、60名T2DM患者、65名合并T2DM的高血压患者和75名对照受试者。
有或无T2DM的高血压患者与对照受试者在年龄、体重指数、收缩压/舒张压、空腹血糖和高密度脂蛋白胆固醇水平上存在显著差异。AGT基因的A20C变体、肾素的MboI、醛固酮的Gly460Trp和内收蛋白的Lys173Arg的等位基因频率和基因型分布在各组之间未发现统计学显著差异(p>0.05)。然而,AGT基因A6G的结果显示,有或无T2DM的原发性高血压患者在等位基因和基因型频率上存在显著差异(p<0.001)。
在RAAS基因的五个多态性中,只有AGT基因的A6G变体在马来西亚原发性高血压和2型糖尿病患者中具有显著相关性。因此,AGT基因的A6G多态性可能是马来西亚受试者患原发性高血压(无论有无T2DM)易感性增加的潜在遗传标记。