Objective: To investigate the relationship of four single nucleotide polymorphism (SNP) haplotypes in the angiotensinogen (AGT) gene to the primary hypertension with or without cerebral infarction in the Li nationality of Hainan, China.
Methods: Total 300 subjects were allocated into three different groups: Group 1, 100 patients who have primary hypertension; Group 2, 100 patients who have primary hypertension with cerebral infarction; and control group, 100 healthy individuals. The genotypes of all subjects were determined by PCR-sequencing to analyze the four polymorphisms at position -152 (G-A), -20 (A-C), -18 (C-T), and -6 (A-G) in the promoter region of AGT.
Results: The frequencies of CT genotype of AGT-18 and T allele in Group 1 (P = 0.003, P = 0.004) and Group 2 (P = 0.002, P = 0.002) were both significantly higher than in healthy controls. The frequency of G allele of AGT-6 was significantly higher in Group 2 than in the control group (P = 0.016), while there is no significant difference between Group 1 and the control. Haplotype analysis revealed that H6 haplotype frequency which included -20C and -6G was significantly increased in Group 2 (P = 0.003) compared with the control group, while H5 haplotype frequency which included -20C and -18T was significantly increased in Group 1 (P = 0.006) versus the control.
Conclusion: The -20 (A-C) and -18 (C-T) of the AGT may play an important role in pathogenesis of primary hypertension; and -20 (A-C), -18 (C-T), and -6 (A-G) may be the genetic risk factors for the onset of primary hypertension with cerebral infarction in the Li nationality of Hainan, China.
目的: 研究血맜紧张素原基因 (angiontensinogen, AGT)4 个位点的单核苷酸多态及其构成的单倍型与海南黎族原发性高血压及原发性高血压并发脑梗死的相关性。
方法: 选择海南黎族人群为研究对象, 利用 PCR 直接测序法, 在 100 例原发性高血压患者、 100 例原发性高血压并脑梗死患者和 100 例健康对照者中, 对 AGT 基因启动子区域的 −152(G-A), −20(A-C), −18(C-T), −6(A-G) 多态进行基因分型。
结果: C-18T 多态的基因型和 T 等位基因频率分布在原发性高血压组 (P = 0.003, P = 0.004) 和原发性高血压并脑梗死组 (P = 0.002, P = 0.002) 均比健康对照组显著增高。 −6(A-G) 多态的 G 等位基因频率在原发性高血压并脑梗死组显著高于健康对照组 (P = 0.016), 而与原发性高血压组比较无显著性差异。 单倍型分析提示, 由 −20C 和 −18T 构成的 H5 单倍型在原发性高血压组中增加, 与对照组相比有显著性差异 (P = 0.006); 而由 −20C 和 −6G 构成的 H6 单倍型在原发性高血压并脑梗死组中明显增加, 与对照组相比有显著性差异 (P = 0.003)。
结论: 在海南黎族人群中, AGT 基因的 −20(A-C), −18(C-T) 多态可能对原发性高血压的发病起了重要作用; −20(A-C), −18(C-T) 和 −6(A-G) 多态可能是原发性高血压并脑梗死发病的遗传危险因素。