高血压定位区域犬尿氨酸酶基因多态性与高血压病相关  

A polymorphism of kynureninase gene in a hypertensive candidate chromosomal region is associated with essential hypertension

作　　者：张怡[1] 张奎星[1] 何鑫[1] 袁文涛 王谷亮[1] 茅守玉[1] 高平进[1] 黄薇 朱鼎良[1] 

机构地区：[1]上海第二医科大学附属瑞金医院 上海市高血压研究所 医学基因组学国家重点实验室 上海市血管生物学重点实验室,现在山东省立医院心内科200025 [2]国家人类基因组南方研究中心

出　　处：《中华心血管病杂志》2005年第7期588-591,共4页Chinese Journal of Cardiology

基　　金：国家"十五"科技攻关项目(2002BA711A05);国家自然科学基金资助项目(30270545)

摘　　要：目的检测中国汉族人群高血压病定位区域2q14-q23内犬尿氨酸酶基因(kynureninase,KYNU)调控区和编码区的单核苷酸多态性(singlenucleotidepolymorphism,SNP)及与高血压病的相关性。方法采用直接测序法检测KYNU基因启动子区和外显子序列中的SNP。应用变性高效液相色谱分析(DHPLC)技术对位于编码区且改变氨基酸编码的Lys412Glu(A/G)多态在456例高血压病患者和430例正常对照者中进行分型和关联研究。结果共检测得KYNU基因的16个SNP,其中启动子区6个,编码区2个(均改变氨基酸编码)。Lys412Glu多态基因型分布(χ2=6·693,P=0·035)和等位基因频率分布(χ2=4·188,P=0·041)在高血压病组和正常对照组间差异均有统计学意义,Lys412Glu等位基因频率分布在男性高血压病组和正常对照组间差异有统计学意义(χ2=4·424,P=0·035)。结论中国汉族高血压病定位区域内KYNU基因Lys412Glu多态可能与高血压病相关。Objective To identify single nucleotide polymorphisms （SNP） in the regulatory and coding regions of human kynureninase （KYNU） gene in a hypertensive candidate chromosomal region 2q14q23 of Han Chinese, and to investigate the relationship between polymorphisms in KYNU and essential hypertension. Methods The SNPs in the promoter region and exons of the KYNU gene were detected by direct DNA sequencing. Genotyping of the nonsynonymous Lys412Glu （A/G） polymorphism was performed by DHPLC technology in 456 hypertensive patients and 430 normal controls. Results Sixteen SNP were identified in the KYNU gene, including 6 in the regulatory region and 2 in the coding region （ both of them lead to substitution of amino acid）. Significant differences between hypertensive patients and normal controls were observed for the distribution of alleles （ x^2 = 6. 693, P = 0. 035 ） and genotypes （ x^2 = 4. 188, P = 0. 041 ） of the Lys412Glu polymorphism in all subjects, and for the distribution of alleles in the subgroup of men （x^2 = 4.424, P = 0. 035 ）. Conclusion The Lys412Glu polymorphism of the KYNU gene in a hypertensive candidate chromosomal region is associated with essential hypertension in Han Chinese.

关 键 词：高血压 基因 多态性 单核苷酸 高血压病患者 酶基因多态性 犬尿氨酸 相关性 变性高效液相色谱分析 中国汉族人群 基因启动子区 

分 类 号：R544.1[医药卫生—心血管疾病] R363.21[医药卫生—内科学]