Molecular Genetic Study of Hypertension

Abstract

隨著社會的發展，高血壓的盛行率也跟著升高。數種家族性高血壓已被確定由單基因 突變所造成。這些研究也為高血壓與基因遺傳有關奠下了證據。本態性高血壓被認為 是由多種基因的變異與環境的互動所造成。由於生理與血壓調控有關的基因稱為候選 基因，大多數本態性高血壓的基因研究在於尋找本態性高血壓和候選基因的相關性。 已有報告本態性高血壓與少數候選基因，例如血管張力素原基因，具有有意義的相關 ；然而其相關性仍因種族而有差別。也有利用多個標幟 ( markers) 進行全基因體掃 瞄，並發現數個與本態性高血壓相關的局部區域 (locus)；它們分佈於染色體2p，2q ，5q，6q，15q，17，和18q 等。一般預期高血壓動物之基因研究將有助於尋找本態 性高血壓的致病基因，目前已有約二十個大鼠之高血壓相關的局部區域被定位。高血 壓的基因研究將有助於高血壓的早期診斷、高血壓及心臟血管危險因子的分析、以及 未來更個人化的治療。然而我們也要瞭解高血壓基因研究的複雜性而且高血壓的基因 變異可能因種族而有差異。Hypertension is a rising problem in the developed countries. Some rare familial hypertensive syndromes have been found to be caused by monogenic mutations. Essential hypertension is generally regarded as a complex genetic trait caused by multiple genes. The polygenic effects on blood pressure are modulated by gene-gene and gene- environment interactions. Most investigations for genetic causes of essential hypertension were approached with candidate genes, and a few candidate genes, such as angiotensinogen gene, were reported to be associated with essential hypertension, though the reports from different populations were still conflicting. Genome-wide scans with multiple markers have mapped several loci associated with blood pressure. The loci reported were on chromosomes 2p, 2q, 5q, 6q, 15q, 17, and 18q respectively . However, to date, no genotype had been conclusively linked to essential hypertension. It has long been hoped that genetic research on hypertensive animals, such as rats, will facilitate our understanding of the genetics of human essential hypertension. So far, more than twenty loci were reported to be associated with blood pressure in rats. More understanding of the genetic basis of essential hypertension should be possible in the future and would be expected to help earlier diagnosis, more effective risk factor assessment and more individualized treatment of hypertension. However, the difficulty of genetic analysis for essential hypertension and the possibility of inter- population differences in genetic factors should be kept in mind.