高血压病患者β_2-肾上腺素能受体基因5′-调控区单核苷酸多态性研究

Study on distribution of single nucleotide polymorphism in 5′- regulatory region of β_ 2 adrenoceptor gene in hypertensives

目的 研究中国人β2 肾上腺素能受体 (β2 AR)基因 5′ 调控区部分序列单核苷酸多态性(SNP) ,探讨这些SNP与高血压病的关系。方法 应用荧光标记自动测序法 ,测定 β2 AR基因 5′ 调控区序列 ,确定单核苷酸多态位点及类型 ;通过聚合酶链式反应 限制片段长度多态性 (PCR RFLP)法对来自安徽大别山地区的正常血压和高血压人群进行SNP基因分型。结果 5′ 调控区 1.3kb范围内共检出 2个SNP ,均为G→A碱基转换 ,分别位于距编码区起始位点上游 10 2 3和 6 5 4碱基处。各SNP的基因型频率符合Hardy Weinberg平衡。位于 10 2 3处的SNP基因型GG、GA、AA频率在正常血压和重度高血压人群中的分布存在显著差异 (χ2 =9.5 3,df=2 ,P <0 .0 1) ,重度高血压组AA频率为2 8 13% ,显著高于正常对照组的 7.5 3% (χ2 =9.2 1,df=1,P <0 .0 1)。结论 β2 AR基因 10 2 3位SNP可能与重度高血压相关 ,提示 β2

Objective To detect single nucleotide polymorphisms (SNP) existing in 5′ regulatory region of β 2 adrenoceptor (β 2 AR) gene and to investigate their associations with hypertension. Methods β 2 AR gene was sequenced by fluorescent labeling automatic sequencing method in unrelated Chinese Han population distributed in Dabie Mountain in Anhui Province. Genotypes of the SNP were typed by PCR RFLP method. Results Two SNP of 1.3 kb long were identified at position 1023 and 654 respectively. They were both G→A substitution. The frequency of genotype of the two SNP complied well with the Hardy Weinberg equilibrium. The distribution of the SNP genotype AA, GA and GG at position 1023 in the severe hypertension group was significantly different from that in normal group (χ 2=9.53, df=2, P <0.01), AA frequency is significantly higher in the severe hypertension group than in the normal group (χ 2=9.21, df=1, P <0.01). Conclusion The SNP at locus 1023 of human β 2 AR gene is associated with severe hypertension in Chinese Han population.