An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension.
An ancestral variant of Secretogranin II confers regulation by PHOX2 transcription factors and association with hypertension.
复制标题
Secretogranin II 的祖先变体可通过 PHOX2 转录因子进行调节并与高血压相关。
DOI：
10.1093/hmg/ddm123
复制
发表时间：
2007
影响因子：
3.5
通讯作者：
Hamilton,BruceA
中科院分区：
文献类型：
--
作者：
Wen,Gen;Wessel,Jennifer;Zhou,Weidong;Ehret,GeorgB;Rao,Fangwen;Stridsberg,Mats;Mahata,SushilK;Gent,PeterM;Das,Madhusudan;Cooper,RichardS;Chakravarti,Aravinda;Zhou,Huilin;Schork,NicholasJ;O'connor,DanielT;Hamilton,BruceA
Granins regulate secretory vesicle formation in neuroendocrine cells and granin-derived peptides are co-released with neurotransmitters as modulatory signals at sympathetic sites. We report evidence for association between a regulatory polymorphism inSecretogranin II(SCG2) and hypertension in African-American subjects. The minor allele is ancestral in the human lineage and is associated with disease risk in two case–control studies and with elevated blood pressure in a separate familial study. Mechanistically, the ancestral allele acts as a transcriptional enhancer in cells that express endogenousScg2, whereas the derived allele does not. ARIX (PHOX2A) and PHOX2B are identified as potential transactivating factors by oligonucleotide affinity chromatography and mass spectrometry and confirmed by chromatin immunoprecipitation. Each of these transcription factors preferentially binds the risk allele, bothin vitroandin vivo. Population genetic considerations suggest positive selection of the protective allele within the human lineage. These results identify a common regulatory variation inSCG2and implicate granin gene expression in the control of human blood pressure and susceptibility to hypertension.
