研究背景
近年來的研究發現許多人類基因表現和基因多型性（genetic polymorphism）可能參與高血壓的致病機轉，其中包括礦物類皮質激素結受器（mineralocorticoid receptor）和醛固酮合成?（aldosterone synthase）。本研究的目的在於分析台灣族群之礦物類皮質激素結受器和醛固酮合成?基因多型性的分佈，並且分析這些基因多型性和本態性高血壓（essential hypertension）、心臟重塑造（cardiac remodeling）之間的關聯。
研究方法
從受試者的週邊血液中抽取DNA進行聚合酵素連鎖反應 - 限制片段長度多型性分析（polymerase chain reaction - restriction fragment length polymorphism analysis），分析礦物類皮質激素結受器基因於G3514C、A4582C和醛固酮合成?基因（CYP11B2）於T-344C段的基因多型性，並且和臨床血壓數值、心臟超音波測量數據進行統計分析。
研究結果
本研究總共收納了192位正常血壓和514位高血壓門診受試者，平均年齡65.32 ± 11.43歲。統計分析發現正常血壓和高血壓受試者在礦物類皮質激素結受器（G3514C、A4582C）和CYP11B2基因T-344C段基因多型性的分佈上沒有顯著的差異（p = 0.583、p = 0.215和p = 0.523）；在心臟超音波的測量數據上也沒有顯著差別。但是，攜帶CYP11B2基因T/T基因型（genotype）的女性，相較於攜帶T/C或C/C基因型的女性，有比較高的比例會有高血壓（p = 0.045）。此外，攜帶C-對偶基因（C-allele）的女性正常血壓受試者，其心臟超音波測量數據，尤其是左心室舒張末期直徑（left ventricular end-diastolic diameter，LVEDD）和左心室收縮末期直徑（left ventricular end-systolic diameter，LVESD），相較於攜帶T/T基因型者有顯著的減少，p 值分別為0.036和0.043。另外，女性高血壓組中攜帶C-對偶基因者其左心室質量（left ventricular mass）和左心房直徑（left atrial diameter）明顯大於T/T型，p = 0.0215和p = 0.0081。這種差異在男性受試者中並不存在。
結論
根據本研究結果推測，CYP11B2基因T-344C段攜帶C-對偶基因的女性正常血壓受試者受到某些保護因子的作用，預防左側心臟結構的重塑造。這些保護因子的產物和屬性，需要更多的研究和探討。
Background
Recent genetic studies have discovered the involvement of numerous genetic loci in the pathogenesis and maintenance of hypertension, including genes and polymorphisms related to mineralocorticoid receptor and aldosterone synthesis. The aim of this study was to evaluate the genotypic distribution of mineralocorticoid receptor and CYP11B2 T-344C polymorphisms in a Taiwanese population, and to establish their relationship with essential hypertension and cardiac remodeling.
Methods
Genomic DNA extracted from peripheral blood samples was subjected to polymerase chain reaction - restriction fragment length polymorphism analysis for the mineralocorticoid receptor loci, G3514C and A4582C, and CYP11B2 T-344C. The genetic distribution of these genes and the association with blood pressure and echocardiographic measurements were statistically analyzed.
Results
A total of 192 normotensive and 514 hypertensive Taiwanese outpatients were recruited with a mean age of 65.32 ± 11.43 years. Statistical analyses revealed no significant differences in the genetic distribution of mineralocorticoid receptor (G3514C, A4582C) and CYP11B2 T-344C polymorphisms between normotensive and hypertensive outpatients, nor were there differences in the echocardiographic measurements between these two groups (p = 0.583, p = 0.215, and p = 0.523). In the subgroup analysis, female outpatients with the T/T genotype were more likely to have hypertension (p = 0.045), as compared to those with T/C or C/C genotypes. In addition, female normotensive outpatients carrying C-allele had a significant lesser degree of left heart structural changes, particularly with left ventricular end-diastolic diameter (p = 0.036) and left ventricular end-systolic diameter (p = 0.043). Besides, female hypertensive outpatients carrying C-allele had a significant greater left ventricular mass (p = 0.0215) and left atrial diameter (p = 0.0081) compared to T/T genotype. Such differences were not observed in the general or male population.
Conclusions
Our data suggests that there is a protective mechanism in female normotensive outpatients carrying C-alleles, preventing them from having left heart structural remodeling. The factors and functions underlying this protective mechanism need to be further elucidated.
