原发性高血压患者G蛋白信号转导调节蛋白-2基因的测序分析

摘要

Objective To investigate the new genetic variations of regulator of G-protein signalling 2 (RGS2) gene in Kazakh hypertensives. Methods Totally 94 Kazakh patients with essential hypertension were enrolled and genomie DNA was extracted from their peripheral blood leukocytes. All the exon regions and their flanking sequences of RGS2 were directly sequenced. Results We identified 13 variants including 5 commonsingle nucleotide polymorphisms with a minor allele frequency over 5％ single nucleotide polymorphisms and 8 novel variations in 94 Kazakh hypertensives. Among these variations, 2 were in the introns and 7 in the promoter region. One subject had a G-to-C substitution at nucleotide 54 in exon 1, which lead to an amino acid substitution from K-to-N at position 18; another individual had an A-to-G substitution at nucleotide 2422 in exon 5, resulting in an amino acid from Y-to-C at position 178. Among eight common single nucleotide polymorphisms, -638A ＞G, -395G ＞C, 1891-1892TC I/D, and 2971G ＞ C, and -43A ＞ T and 2297A ＞ G were in tight linkage disequilibrium with an r-square of more than 0. 8, respectively. Conclusions The variants and their frequencies in RGS2 gene in Kazakh hypertensives may have ethnic differences when compared with other populations.The frequencies of the mutations are low in this population, and whether they influence blood pressure regulation requires further functional experiments.%目的 在新疆哈萨克族原发性高血压患者中进行测序分析,寻找新的G蛋白信号转导调节蛋白-2基因序列变异.方法 选择新疆哈萨克族原发性高血压患者94例,抽取静脉血提取DNA.采用PcR产物直接测序法,对94例样本的外显子区及其侧翼序列进行测序,检测G蛋白信号转导调节蛋白.2基因变异情况.结果 94例样本共检测出13个变异位点,包括5个常见变异和8个新发现变异位点,其中启动子区变异7个,内含子2个,外显子1和外显子5各检出1个新的错义突变(K18N和Y178C);-638A>G、-395G>C、1891-1892TC I/D和2971G>C以及-43A>T和2297A>G之间存在连锁不平衡关系(r<'210.8).结论 RGS2基因在新疆哈萨克族高血压患者中检出的变异位点及频率存在种族特异性,外显子区的错义突变频率较低,是否影响血压调节需进一步的功能验证.