CAJ | 학술논문

目的：了解糖尿病患者hOGG1基因Ser326Cys位点多态性与冠脉病变之间的关系。方法：入选行冠状动脉造影术的糖尿病患者共323例，应用聚合酶链式反应－限制性片段长度多态性（ PCR－RFLP）技术检测每位患者的hOGG1基因Ser326Cys位点多态性。同时检测患者血糖、血脂、肾功能等生化指标。根据患者hOGG1基因Ser326Cys多态性分为3组：Cys／Cys基因型（85例）、Ser／Ser基因型（121例）和Ser／Cys基因型（117例）。由2名心血管医师对冠脉造影图像进行分析，按评判标准统计冠脉病变支数、病变复杂程度、Gensini评分和SYNTAX评分。分析hOGG1基因Ser326Cys多态性对hOGG1 mRNA表达和血8－OHdG水平的影响，以及对冠脉病变产生的影响。结果：（1）Cys／Cys基因型、Ser／Ser基因型和Ser／Cys基因型血8－OHdG水平差异显著（P＜0．05）。组间两两比较，Cys／Cys基因型高于Ser／Ser基因型和Ser／Cys基因型，差异有统计学意义（ P＜0．05）；而 Ser／Ser基因型与Ser／Cys基因型比较，差异不显著（P＞0．05）。（2）Cys／Cys基因型hOGG1 mRNA的表达低于Ser／Ser基因型和Ser／Cys基因型（P＜0．05）。而Ser／Ser基因型与Ser／Cys基因型比较，hOGG1 mRNA表达差异不显著（P＞0．05）。（3） Cys／Cys基因组出现3支病变的概率为37．6％，Ser／Cys基因型出现冠脉1支病变的概率为35．9％，但3组病变支数概率的差异均不显著（P＞0．05）。（4）Cys／Cys基因型的Gensini和SYNTAX评分分别为48．7±15．3和39．5±17．2，冠脉复杂病变概率为73．0％，均高于Ser／Ser基因型和Ser／Cys基因型，差异显著（ P＜0．05）。而Ser／Ser基因型和Ser／Cys基因型之间比较，差异均无统计学意义（P＞0．05）。结论： hOGG1基因Ser326Cys位点多态性与糖尿病患者冠脉病变有关，其中Cys／Cys基因型与病变严重程度有一定关系，其机制可能是Cys／Cys基因型的hOGG1表达水平下降，识别和切除DNA双链中的8－OHdG 能力降低，修复DNA氧化损伤的能力下降，从而加速动脉粥样硬化的发生、发展。目的：瞭解糖尿病患者hOGG1基因Ser326Cys位點多態性與冠脈病變之間的關繫。方法：入選行冠狀動脈造影術的糖尿病患者共323例，應用聚閤酶鏈式反應－限製性片段長度多態性（ PCR－RFLP）技術檢測每位患者的hOGG1基因Ser326Cys位點多態性。同時檢測患者血糖、血脂、腎功能等生化指標。根據患者hOGG1基因Ser326Cys多態性分為3組：Cys／Cys基因型（85例）、Ser／Ser基因型（121例）和Ser／Cys基因型（117例）。由2名心血管醫師對冠脈造影圖像進行分析，按評判標準統計冠脈病變支數、病變複雜程度、Gensini評分和SYNTAX評分。分析hOGG1基因Ser326Cys多態性對hOGG1 mRNA錶達和血8－OHdG水平的影響，以及對冠脈病變產生的影響。結果：（1）Cys／Cys基因型、Ser／Ser基因型和Ser／Cys基因型血8－OHdG水平差異顯著（P＜0．05）。組間兩兩比較，Cys／Cys基因型高于Ser／Ser基因型和Ser／Cys基因型，差異有統計學意義（ P＜0．05）；而 Ser／Ser基因型與Ser／Cys基因型比較，差異不顯著（P＞0．05）。（2）Cys／Cys基因型hOGG1 mRNA的錶達低于Ser／Ser基因型和Ser／Cys基因型（P＜0．05）。而Ser／Ser基因型與Ser／Cys基因型比較，hOGG1 mRNA錶達差異不顯著（P＞0．05）。（3） Cys／Cys基因組齣現3支病變的概率為37．6％，Ser／Cys基因型齣現冠脈1支病變的概率為35．9％，但3組病變支數概率的差異均不顯著（P＞0．05）。（4）Cys／Cys基因型的Gensini和SYNTAX評分分彆為48．7±15．3和39．5±17．2，冠脈複雜病變概率為73．0％，均高于Ser／Ser基因型和Ser／Cys基因型，差異顯著（ P＜0．05）。而Ser／Ser基因型和Ser／Cys基因型之間比較，差異均無統計學意義（P＞0．05）。結論： hOGG1基因Ser326Cys位點多態性與糖尿病患者冠脈病變有關，其中Cys／Cys基因型與病變嚴重程度有一定關繫，其機製可能是Cys／Cys基因型的hOGG1錶達水平下降，識彆和切除DNA雙鏈中的8－OHdG 能力降低，脩複DNA氧化損傷的能力下降，從而加速動脈粥樣硬化的髮生、髮展。
목적：료해당뇨병환자hOGG1기인Ser326Cys위점다태성여관맥병변지간적관계。방법：입선행관상동맥조영술적당뇨병환자공323례，응용취합매련식반응－한제성편단장도다태성（ PCR－RFLP）기술검측매위환자적hOGG1기인Ser326Cys위점다태성。동시검측환자혈당、혈지、신공능등생화지표。근거환자hOGG1기인Ser326Cys다태성분위3조：Cys／Cys기인형（85례）、Ser／Ser기인형（121례）화Ser／Cys기인형（117례）。유2명심혈관의사대관맥조영도상진행분석，안평판표준통계관맥병변지수、병변복잡정도、Gensini평분화SYNTAX평분。분석hOGG1기인Ser326Cys다태성대hOGG1 mRNA표체화혈8－OHdG수평적영향，이급대관맥병변산생적영향。결과：（1）Cys／Cys기인형、Ser／Ser기인형화Ser／Cys기인형혈8－OHdG수평차이현저（P＜0．05）。조간량량비교，Cys／Cys기인형고우Ser／Ser기인형화Ser／Cys기인형，차이유통계학의의（ P＜0．05）；이 Ser／Ser기인형여Ser／Cys기인형비교，차이불현저（P＞0．05）。（2）Cys／Cys기인형hOGG1 mRNA적표체저우Ser／Ser기인형화Ser／Cys기인형（P＜0．05）。이Ser／Ser기인형여Ser／Cys기인형비교，hOGG1 mRNA표체차이불현저（P＞0．05）。（3） Cys／Cys기인조출현3지병변적개솔위37．6％，Ser／Cys기인형출현관맥1지병변적개솔위35．9％，단3조병변지수개솔적차이균불현저（P＞0．05）。（4）Cys／Cys기인형적Gensini화SYNTAX평분분별위48．7±15．3화39．5±17．2，관맥복잡병변개솔위73．0％，균고우Ser／Ser기인형화Ser／Cys기인형，차이현저（ P＜0．05）。이Ser／Ser기인형화Ser／Cys기인형지간비교，차이균무통계학의의（P＞0．05）。결론： hOGG1기인Ser326Cys위점다태성여당뇨병환자관맥병변유관，기중Cys／Cys기인형여병변엄중정도유일정관계，기궤제가능시Cys／Cys기인형적hOGG1표체수평하강，식별화절제DNA쌍련중적8－OHdG 능력강저，수복DNA양화손상적능력하강，종이가속동맥죽양경화적발생、발전。
[ABSTRACT]AIM:Tostudytherelationshipbetweenhuman8-oxoguanineglycosylase1(hOGG1)gene Ser326Cys polymorphism and severity of coronary artery lesions in the patients with diabetes mellitus .METHODS: We retrospectively analyzed 323 patients with diabetic mellitus receiving coronary angiography .These patients underwent the test of polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP), and were divided into Cys/Cys genotype (n=85), Ser/Ser genotype (n=121) and Ser/Cys genotype (n=117) according to the results of PCR-RFLP. All clinical data including history of diseases , complications and biochemical markers , such as blood glucose , blood lipids and so on, were recorded.hOGG1 mRNA and 8-hydroxydeoxyguanosine (8-OHdG) were measured by RT-PCR and ELISA, respectively.The results of coronary angiography such as number and severity of coronary artery with lesions were analyzed by 2 cardiovascular physicians .Gensini score and SYNTAX score were also detected by the unitary criteria .RE-SULTS:(1)8-OHdG in Cys/Cys genotype was higher than that in Ser /Ser genotype and Ser/Cys genotype (P<0.05), but there was no statistical difference between Ser /Ser genotype and Ser/Cys genotype (P>0.05).(2)hOGG1 mRNA ex-pression in Cys/Cys genotype was lower than that in Ser/Ser genotype and Ser/Cys genotype (P<0.05), and no statistical difference between Ser/Ser genotype and Ser/Cys genotype (P>0.05) was observed.(3)The probability of triple vessel lesions in Cys/Cys genotype was high and the probability of single vessel lesions in Ser /Cys genotype was low , but the difference among 3 genotypes was not statistically significant (P>0.05).(4)Gensini score and SYNTAX score in Cys/Cys genotype were 48.7 ±15.3 and 39.5 ±17.2, respectively, and the ratio of complex lesions in Cys/Cys genotype was 73.0%.These scores and the ratio of complex lesions were higher than the other 2 genotypes (P<0.05), and no statisti-cal difference between Ser/Ser genotype and Ser/Cys genotype was observed (P>0.05).CONCLUSION:hOGG1 gene Ser326Cys polymorphism has relationship with coronary artery lesions in the patients with diabetes mellitus and Cys /Cys genotype might have some impacts on the severity of lesions .The mRNA expression of hOGG1 in the patients with diabetes mellitus carrying Cys/Cys genotype is lower than that in the patients carrying the other 2 genotypes , then decreases the abil-ity of identification and removal of 8-OHdG and the capacity of repairing DNA oxidative damage , and accelerates the devel-opment of atherosclerosis .