| 摘要: | 心臟血管疾病為台灣地區常見慢性病之ㄧ，2005年所公佈的台灣十大死因顯示，心臟疾病排名第三位，而冠狀動脈心臟病則是心血管疾病重要的病因。流行病學研究顯示，許多遺傳和環境因子包括年齡、性別、抽菸、飲食習慣、高血壓、糖尿病和家族史都與冠狀動脈心臟病有關，而氧化壓力對於冠心病發生的病原上亦扮演重要角色，但證據有限。抗氧化壓力基因多形性可能修飾氧化壓力對冠心病的影響，而影響個人對動脈粥樣硬化或心血管疾病的易感性。本研究要探討抗氧化壓力之基因多形性（MnSOD、CAT、GPx1）和氧化壓力生物標記之蛋白質羰基濃度與冠狀動脈心臟病之相關性。
研究對象選自基隆長庚醫院接受心導管門診檢查之民眾，病例組為經由醫師詳細診斷，發現具有一條以上冠狀動脈阻塞超過50％者。對照組需為非癌症之病人，且並未發現有冠狀動脈阻塞的現象。最終病例組有663位，對照組有413位，合計1076名研究個案進入統計分析。並使用自填式問卷，其內容包含基本人口學資料、生活習慣、人格特質與家族病史。抽取血液以進行MnSOD Val-9Ala、CAT C-262T和GPx1 Pro198Leu之基因多形性分析，進一步利用ELISA之方法分析血漿蛋白質羰基濃度。
研究結果顯示，吸菸習慣與飲酒習慣對於冠狀動脈心臟病的發生有顯著相關性，有吸菸者罹患冠心病之相對風險為未吸菸者之3.06倍（95% CI = 2.04-4.59），有飲酒者的相對風險較未飲酒者降低48％（OR = 0.52，95% CI = 0.35-0.77），皆具統計學上顯著差異（p < 0.05）。MnSOD帶有Ala對偶基因者相較於帶有Val/Val者，有1.8倍之風險的到冠狀動脈心臟病（OR = 1.81，95% CI = 1.05-3.10），而CAT與GPx1基因多形性與冠心病發生之相關性，並無發現顯著差異。但在將性別、年齡分組後發現，男性和年輕族群帶有MnSOD、CAT變異型對偶基因，有較高的風險罹患冠心病，尤其是男性個案MnSOD基因為Ala對偶基因者風險較Val/Val為最高（OR = 2.43，95% CI = 1.16-5.11）。觀察三個基因的共同作用，與三個基因皆為常見之基因型相較，有一基因變異型和二個者，風險分別為1.63倍（95% CI = 1.03-2.58）和2.40倍（95% CI = 0.73-7.88）。蛋白質羰基平均濃度，在病例與對照兩組之間並無顯著差異。
綜合言之，吸菸、飲酒、年齡、性別、糖尿病、家族史與血脂異常與冠狀動脈心臟病之發生有相關性。MnSOD基因多型性與發生冠心病有關。蛋白質羰基濃度並未與冠心病有相關。
Coronary heart disease (CHD) is the most prevalent heart disease and the third leading cause of deaths in 2005 for Taiwanese population. Epidemiological studies have shown that genetic and environmental factors, including age, gender, cigarette smoking, diet, hypertension, diabetes and family history, are related to CHD. Oxidative stress also plays an important role in the etiology of this disease, but evidences are limited. Polymorphism of antioxidant genes may modify the CHD risk from oxidative stress, and contribute to the susceptibility for atherosclerosis or cardiovascular disease. Our study was conducted to examine the association between polymorphisms (MnSOD, CAT, GPx1) of antioxidant genes, plasma protein carbonyls (a biomarker of oxidative stress) and risk of coronary heart disease.
Participants were recruited from the Chang Gung Memorial Hospital in Keelung. Cases were angiographically diagnosed with the present of > 50% stenosis in one of the coronary arteries, and controls were with the normal coronary arterises. A total of 663 cases and 413 controls were included in our study. Information on sociodemographic characteristics of study participants were ascertained by a slef-reported questionnaire. Genotypes of MnSOD, CAT, and GPx1 were confirmed by PCR-RFLP methods. We analyzed protein carbonyls by Enzyme-Linked Immunosorbent Assay (ELISA).
Our results showed that cigarette smoking and alcohol comsunption were signifcantlly associated with the risk of coronary heart disease. Compared with non-smoker, the ORs for smokers was 3.06 (95% CI = 2.04-4.59). Drinkers had a 48% decreased risk compared with non-drinkers (OR = 0.52, 95% CI = 0.35-0.77). We also found that individuals carrying the MnSOD Ala allele had 1.8-fold risk of coronary heart disease than those carrying Val/Val genotype (OR = 1.81, 95% CI = 1.05-3.10). However, CAT and GPx1 genotype were not associated with CHD risk. After stratified by gender and age, men or younger subjects inheriting variant genotype of MnSOD and CAT would at higher CHD risk, especially for men having MnSOD Ala allele compared to Val/Val genotype (OR = 2.43，95% CI = 1.16-5.11). Compared to the most common genotypes of the three genes, the ORs for individuals carrying one variant and two variants were 1.63 (95% CI = 1.03-2.58) and 2.40 (95% CI = 0.73-7.88), respectively. However, the protein carbonyl levels were not significantly different between cases and controls.
Our results suggest that cigarette smoking, alcohol drinking, age, sex, diabetes, and dyslipidemia may contribute to the development of coronary heart disease. Genetic polymorphism of MnSOD also play a role in the CHD risk, but plasma protein carbonyls are not associated with the disease risk. |
