Interactive Effects of Two Different Types of Single Nucleotide Polymorphism and Life Style on Intra-and Inter-individual Changes in Intraocular Pressure and Blood Pressure on the basis of the Longitudinal Epidemiological

本研究在流行病学分析的基础上，探讨各种生活方式相关因素、血管紧张素原基因密码子174 （T174M）多态性（AGT174）和线粒体DNA 5178 A/C多态性（MT5178）对个体内及个体间眼压和血压变化的交互作用。研究对象为1999 ~ 2006年水户红十字医院主办的人体干船坞中老年考生。除若干横断面研究外，还进行了随访研究，以流行病学角度分析上述遗传因素、生活方式、眼压（TOP）和血压（BP）的相互关系。得到了以下主要结果，揭示了遗传因素和生活方式的交互作用。饮酒习惯对AGT174患者舒张压（DBP）的影响在M等位基因携带者（MM/TM）和TT纯合子携带者（TT）之间存在差异，显示饮酒习惯与MM/TM患者舒张压（DBP）在横断面和纵向上呈明显的负相关，而在TT中呈正相关。从纵向研究中发现，吸烟习惯、咖啡摄入习惯和高BMI导致的DBP和IOP的时间相关增加在MM/TM中比在tt中更为明显。研究发现，MT5178与习惯性饮酒对血压的影响之间存在显著的横断面关联，在携带MT5178C的男性中，每日饮酒者的收缩压和舒张压明显高于偶尔或不饮酒者，而在携带mt5178a的男性中，饮酒与血压之间没有关联。横断面研究的多元回归分析显示，MT5178A患者吸烟习惯与IOP升高显著相关，MT5178C患者饮酒习惯与IOP升高显著正相关。

The objective of the present study was to clarify the interactive effects of various life style-related factors, angiotensinogen gene codon 174 (T174M) polymorphism (AGT174) and mitochondrial DNA 5178 A/C polymorphism (MT5178) on intra-and inter-individual changes in intraocular pressure and blood pressure on the basis of the epidemiological analyses. The subjects were middle and old-aged examinees of human dry dock conducted under the auspices of Mito Red Cross Hospital between 1999 and 2006. In addition to several cross-sectional studies, the follow-up studies were conducted in order to epidemiologically analyze the interrelations of the aforementioned genetic factors, life style, intraocular pressure (TOP) and blood pressure (BP).The following main results were obtained, revealing the interactive effects of the genetic factors and life style.1. The effects of drinking habit on diastolic blood pressure (DBP) differed between M allele carrier (MM/TM) and TT homozygote carrier (TT) in AGT174, showing clear inverse cross-sectional and longitudinal associations between drinking habit and DBP in MM/TM in contrast with positive associations in TT.2. From the longitudinal studies, it was found that time-related increases in DBP and IOP due to smoking habit, coffee intake habit and high BMI were more evident in MM/TM than in TT.3. A significant cross-sectional association between MT5178 and the effects of habitual drinking on blood pressure was found, showing that systolic and diastolic BP were significantly higher in daily drinkers than in occasional or non-drinkers among men carrying MT5178C, whereas no associations between drinking and BP were found in men carrying MT5178A.4. According to multiple regression analysis in the cross-sectional study, smoking habit was significantly associated with increased IOP in men with MT5178A, while drinking habit was significantly positively associated with IOP in those with MT5178C.