血管紧张素原基因5’端启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性

Relationship between the mononucleotide polymorphism of angiotensinogen gene at 5’ end promoter A-20C and A-6G and essential hypertension in Mongol nationality

目的:分析血管紧张素原基因启动子区A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压的相关性。方法:实验于2005-08/2006-01在北京华大实验室完成。选取对象均为生活在内蒙古乌拉特后旗的蒙古族牧民,三代血亲内无其他民族。采用基因测序技术对内蒙古蒙古族人群中107例原发性高血压患者和108例正常对照者进行A-20C和A-6G基因分型,观察高血压组和正常对照组不同基因型的分布和等位基因频率的差异。结果:①两组受试者在性别、年龄及吸烟、饮酒、体质量指数和临床化验检查指标有较好的匹配(P均>0.05)。②两组血管紧张素原基因A-20C位点AA,AC,CC基因型频率比较差异无显著性意义(高血压组分别为0.51,0.29,0.20;正常对照组分别为0.49,0.28,0.23,χ2=0.395,P=0.529)。A,C等位基因频率比较差异无显著性意义(高血压组分别为0.65,0.35;正常对照组分别为0.63,0.37,χ2=0.015,P=0.904)。③两组血管紧张素原基因A-6G位点AA,AG,GG基因型频率比较差异无显著性意义(高血压组分别为0.50,0.33,0.17;正常对照组分别为0.55,0.34,0.11,χ2=1.924,P=0.165)。A,G等位基因频率比较差异无显著性意义(高血压组分别为0.66,0.34;正常对照组分别为0.72,0.28,χ2=1.728,P=0.189)。④高血压组协同存在血管紧张素原基因A-20C基因型CC时,血管紧张素原基因A-6G基因型GG频率稍高于正常对照组,但差异无显著性意义(χ2=2.395,P=0.122,OR=7.52,95%CI0.014～1.250),高血压组G等位基因明显高于正常对照组(分别为0.37,0.22,χ2=4.658,P=0.034),携带该等位基因的蒙古族人群发生原发性高血压的相对危险度升高(OR=2.80,95%CI1.087～7.271)。结论:血管紧张素原基因A-20C和A-6G单核苷酸多态性与蒙古族人群原发性高血压相关,并可能具有协同作用。

AIM： To investigate the relationship between the mononucleotide polymorphism of angiotensinogen gene at promoter A-20C and A-6G and essential hypertension in Mongol nation population. METHODS： The experiment was performed in the Beijing Huada Laboratory from August 2005 to January 2006. All the subjects lived in Wulatehouqi of Nei Monggol Autonomous Region and they had not other nation in tert-blood relation. Sequencing technique was used to identity A-20C and A-6G genotype in 107 Mongol patients with essential hypertension and 108 Mongol healthy adults of Nei monggol Autonomous Region, at the same time. Distinct genotypic distribution and allele frequency difference were observed between hypertension group and normal control group. RESULTS： （1）Sex, ages, smoking, drinking, body mass index （BMI）, clinic chemical examination had better matching between two groups （P 〉 0.05）. （2）No significant difference was observed in the distribution of genotypes AA, AC, CC at locus A-20C of Mongolians＇ angiotensinogen gene between the two groups （0.51,0.29,0.20 in the hypertension group; 0.49,0.28,0.23 in the normal control group,χ^2=0.395,P=0.529）. There was no significant difference in the gene frequencies of the A and the C allele of the two groups （0.65,0.35 in the hypertension group; 0.63,0.37 in the normal control group,χ^2=0.015,P =0.904）. （3）The distributions of genotypes AA, AG, GG at locus A-6G of angiotensinogen gene did not show significant difference between the two groups （0.50,0.33,0.17 in the hypertension group; 0.55,0.34,0.11 in the normal control group,χ^2=1.924,P =0.165）. There was no significant difference in the frequencies of A and G allele （0.66,0.34 in the hypertension group; 0.72,0.28 in the normal control group,χ^2=1.728,P =0.189）. （4）With genotype CC at locus A-20C of angiotensinogen synergia existing, the frequency of genetype GG at locus A-6G of angiotensinogen was slightly higher in the hypertension group than the normal control group, but there was no significant difference （χ^2=2.395, P =0.122,OR =7.52,95% confidence interval from 0.014-1.250）. The frequency of G allele in the hypertension group was obviously higher than that in the normal control group （0.37,0.22,χ^2 =4.658,P =0.034）. Relative risk of essential hypertension was raised up in Mongol nation population with the allele （OR =2.80,95% confidence interval from 1.087- 7.271）. CONCLUSION： The A-20C and A-6G mononucleotide polymorphism of angiotensinogen gene is associated with essential hypertension in Mongol nation population, and there may be synergy.