急性冠脉综合征中医证候因素及与GNB3基因C825T多态性关系研究
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摘要
目的
本研究遵循临床流行病学的方法和原则,以北京地区汉族患者的临床资料为依据,运用现代统计学方法,对急性冠脉综合征的中医证候因素进行探索;探讨冠状动脉造影、实验室指标和中医证候因素之间的关系,以期为中医微观辨证提供依据;同时探讨G蛋白β3亚单位基因(GNB3)C825T多态性与ACS中医证候关系。
方法
315例临床资料来源于安贞医院的北京地区汉族ACS住院患者,运用因子分析方法,对急性冠脉综合征的中医证候因素进行探索;并研究证候因素在病变支数上分布情况以及各证候因素的Gensini积分差异;运用典则相关分析,对实验室指标(TC、TG、LDL-C、hs-CRP、TNI、HCY、FIB)和中医证候因素的相关性进行探讨;运用LogiStic回归分析方法探讨证候因素的影响因素;对中青年男性和老年男性发病情况的差异进行比较;检测患者G蛋白β3亚单位基因型,并将证候因素按照虚、实分为两组,对C825T多态性与ACS中医虚实证候关系进行研究。
结果
1运用频数统计方法研究ACS患者症状,出现频率前十位的症状按顺序分别是:胸闷、心悸、气短、痛时汗出、口唇紫暗、乏力、针刺样痛、肢麻沉重、腰酸膝软、健忘。
2运用因子分析的方法得到8个ACS中医证候因素为痰浊、血瘀、阳虚、气虚、气滞、寒凝、热蕴、阴虚;患者8个证候因素在性别、年龄组和疾病不同临床分类上的分布在统计学上无显著性差异(P>0.05)。
3 ACS中医证候因素分布与冠状动脉造影有关(P<0.05)。8个证候因素在冠脉病变支数情况上的分布有统计学差异(P=0.007),不同证候因素的Gensini积分不同(P=0.001)。寒凝与血瘀冠脉病变支数较其他证候因素多,Gensini积分值由高至低分别是:寒凝>血瘀>阳虚>热蕴>阴虚>痰饮>气虚>气滞。从本虚角度考虑,随着气虚、阴虚、阳虚,病变程度逐渐加重。寒凝与血瘀在多支病变支数分布和Gensini积分值均较高,说明随着寒凝、血瘀的出现,冠脉病变范围和程度趋于严重.
4典则相关分析提示FIB与气虚、hs-CRP与痰饮、cTNI与寒凝有相关性。
5以进行二值Logistic回归分析气虚、阳虚、血瘀、痰浊的影响因素,发现吸烟年限和心衰病史为血瘀的影响因素;体重指数、西方饮食方式为痰饮的影响因素;高血压家族史、合并高血压病和心功能为阳虚的影响因素;劳累为气虚的影响因素)。
6对中青年男性和老年男性进行对照,发现中青年男性发病与吸烟、西方饮食方式有关,而老年男性与合并高血压病关系密切(P<0.05)。
7 ACS组TT基因型高于对照组,CC基因型低于对照组,差异有统计学意义,T等位基因频率在ACS组显著高于正常对照组(P<0.05)。实证组与对照组相比,在基因频率和等位基因分布两方面均有显著性差异(P=0.018;P=0.004)。实证组与虚证组相比及虚证组与对照组相比,在基因频率和等位基因分布两方面均没有显著性差异(P>0.05)。
8研究TT基因型和T等位基因发生急性冠脉综合征及其ACS实证或虚证的危险度。与对照组相比,ACS组TT基因型和T等位基因发生急性冠脉综合征的0R值大于1(P<0.05),说明TT基因型和T等位基因是ACS的易感基因。实证组与对照组相比0R值大子1(P<0.05),但实证组与虚证组、虚证组与对照组比较,P值均大于0.05,因此尚不能说明TT基因型和T等位基因与ACS实证组或虚证组相关。
结论
1 ACS证候因素为痰浊、血瘀、阳虚、气虚、气滞、寒凝、热蕴、阴虚。
2 ACS中医证候因素与冠状动脉造影病变支数分布和Gensini积分值有关。
3 FIB与气虚;hs-CRP与痰饮;cTNI与寒凝相关。
4吸烟年限和心衰病史为血瘀的影响因素;体重指数、西方饮食方式为痰饮的影响因素;高血压家族史、合并高血压病和心功能为阳虚的影响因素;劳累为气虚的影响因素。
5中青年男性发病与吸烟、西方饮食方式有关,而老年男性与合并高血压病关系密切。
6 GNB3基因C825T多态性T等位基因可能是ACS发病的遗传危险因素之一;未证实与ACS虚、实证候的明确相关性。
Objective
According to the methods and principles of clinical epidemiology,using modern statistical methods,his study probed into the TCM syndrome pattern of ACS sampling from Beijing of Han People.To investigate the relationship between the changes of coronary angiography(CAG),laboratory indices and the types of TCM syndromes,in order to present the basis in microcosmic determination of treatment based on differentiation of syndromes.To explore the relationship between the types of TCM syndromes and G-proteinβ3 submit(GNB3) C825T polymorphisms.
Methods
315 clinical cases diagnosed as ACS hospitaled in Anzhen hospital in Beijing of Han People.Using the factor analysis method,this study explored the types of syndrome.This study explored the realationship between the affection branches and the types of syndrome,compared the difference between Gensini accumulated points also.Using Canonical analysis method,this study investigated the relationship between the laboratory indices(TC、TG、LDL-C、hs-CRP、TNI、HCY、FIB)and the types of syndrome.The influencing factor was analyzed by using Binary-Logistic regresstion. The difference between male whose age＜60 and male whose age≥60 was compared. 103 health adults was enrolled as control group.The relationship between the types of TCM syndromes and GNB3 C825T polymorphisms was investigated.
Results
1.The number of TCM symtorns of ACS in the frenqency was as follows:chest distress,cardiopalmus,short breath,perspiration when chest pain,oral lips cyanosis, lack of power,pricking pain,anesthesia and heavy,waist soreness,loss of memory.
2.Using the factor analysis method,8 types of TCM syndromes were found.There was no significant statistical difference in the gender,age groups,clinical categorization of ACS over the distribution of TCM syndromes(P＞0.05).
3.There were correlations between the types of TCM syndromes and coronary arteriongraphy(P＜0.05).There was significant statistical difference in the number of coronary artery pathologic changes over the distribution of the 8 types of TCM syndromes(P=0.007).The grades of Gensini were different in the different types of TCM syndromes(P=0.001).The accumulation-syndrome of pathogenic cold was more than other syndromes in the number of coronary artery pathologic changes (P＜0.05).The sequence from the first to the last one by the grades of Gensini:the accumulation-syndrome of pathogenic cold＞the syndrome of blood stasis＞the deficiency-syndrome of yang＞heat＞the deficiency-syndrome of yin＞the syndrome of sputum-turbid＞the deficiency-syndrome of qi＞stagnation-syndrome of qi.While consider the deficiency-syndrome of essence,the degree of aeteria coronaria pathologic changes was more and more severious with the appearance of the deficiency-syndrome of qi,the deficiency-syndrome of yin,the deficiency-syndrome of yang.The accumulation-syndrome of pathogenic cold and the syndrome of blood stasis was the more serious than other syndromes,because their numbers of coronary artery pathologic changes and grades of Gensini were both high.
4.Canonical analysis showed that FIB was correlated with the deficiency-syndrome of qi;hs-CRP was correlated with the syndrome of sputum-turbid; cTNI was correlated with the accumulation-syndrome of pathogenic cold.
5.This study investigated the influential factors of such syndromes of ACS:the deficiency-syndrome of qi,the deficiency-syndrome of yang,the syndrome of blood stasis,the syndrome of sputum-turbid.The times of smoking and history of heart failurethe was influential factors of the syndrome of blood stasis.BMI and the western style of diet were the influencing factor of the syndrome of sputum-turbid.Family history of essential hypertension,essential hypertension and heart function were the influencing factor of the deficiency-syndrome of yang.Exertion was the influencing factor of the deficiency-syndrome of qi.
6.Comparing the male those age＜60 and male those age≥60,the male patients those age＜60 were correlated with cigarettes and western style of diet.While the male patients whose age≥60 were correlated with essential hypertension(P＜0.05).
7.The TT gene type of GNB3 was significantly higher in patients of ACS than control group,while CC gene type of GNB3 was significantly lower than control group and TT gene type was significantly higher than control group(P＜0.05).The frequence of T allele was higher than control group(P＜0.05).Comparing with control group, the sthenia syndrome had significant difference both in distribution and frequency of T allele.Those were no significant difference in frequency of TT genotype and T allele in compared the sthenia syndrome with the deficiency syndrome,and compared the deficiency syndrome with the control group(P＞0.05).
8.This study investigated the risk of the appearance of the sthenia syndrome and the deficiency syndrome due to TT genotype or T allele.Those carriers of the TT genotype and T allele of ACS were easier to become ACS than the control group(OR＞1,P＜0.05).TT genotype and T allele may be the predisposing genes to ACS.The value of OR in the sthenia syndrome was exceed 1 than the control group(P＜0.05). But comparing not only control group but also the sthenia syndrome,the value of P in the deficiency syndrome was larger than 0.5.For this reason,the TT genotype and T allele were not affirmed the association with the sthenia syndrome and deficiency syndrome of ACS.
Conclusion
1.The syndromes of ACS:the syndrome of sputum-turbid,the syndrome of blood stasis,the deficiency-syndrome of yang,the deficiency-syndrome of qi,the stagnation-syndrome of qi,the accumulation-syndrome of pathogenic cold,heat,the deficiency-syndrome of yin.
2.There were correlations between the types of TCM syndromes with coronary arteriongraphy.
3.FIB was correlated with the deficiency-syndrome of qi,hs-CRP was correlated with the syndrome of sputum-turbid,cTnI was correlated with the accumulation-syndrome of pathogenic cold.
4.The times of smoking and history of heart failurethe was influential factors of the syndrome of blood stasis.BMI and the western style of diet were the influencing factor of the syndrome of sputum-turbid.Family history of essential hypertension, essential hypertension and heart function were the influencing factor of the deficiency-syndrome of yang.Exertion was the influencing factor of the deficiency-syndrome of qi.
5.The male patients whose age＜60 were correlated with cigarettes and western style of diet.While the male patients whose age≥60 were correlated with essential hypertension.
6.The TT allele C825T of GNB3 gene may be one of the genetic risk factors of ACS.The TT genotype and T allele were not affirmed the association with the sthenia syndrome and deficiency syndrome of ACS.
本研究遵循临床流行病学的方法和原则,以北京地区汉族患者的临床资料为依据,运用现代统计学方法,对急性冠脉综合征的中医证候因素进行探索;探讨冠状动脉造影、实验室指标和中医证候因素之间的关系,以期为中医微观辨证提供依据;同时探讨G蛋白β3亚单位基因(GNB3)C825T多态性与ACS中医证候关系。
方法
315例临床资料来源于安贞医院的北京地区汉族ACS住院患者,运用因子分析方法,对急性冠脉综合征的中医证候因素进行探索;并研究证候因素在病变支数上分布情况以及各证候因素的Gensini积分差异;运用典则相关分析,对实验室指标(TC、TG、LDL-C、hs-CRP、TNI、HCY、FIB)和中医证候因素的相关性进行探讨;运用LogiStic回归分析方法探讨证候因素的影响因素;对中青年男性和老年男性发病情况的差异进行比较;检测患者G蛋白β3亚单位基因型,并将证候因素按照虚、实分为两组,对C825T多态性与ACS中医虚实证候关系进行研究。
结果
1运用频数统计方法研究ACS患者症状,出现频率前十位的症状按顺序分别是:胸闷、心悸、气短、痛时汗出、口唇紫暗、乏力、针刺样痛、肢麻沉重、腰酸膝软、健忘。
2运用因子分析的方法得到8个ACS中医证候因素为痰浊、血瘀、阳虚、气虚、气滞、寒凝、热蕴、阴虚;患者8个证候因素在性别、年龄组和疾病不同临床分类上的分布在统计学上无显著性差异(P>0.05)。
3 ACS中医证候因素分布与冠状动脉造影有关(P<0.05)。8个证候因素在冠脉病变支数情况上的分布有统计学差异(P=0.007),不同证候因素的Gensini积分不同(P=0.001)。寒凝与血瘀冠脉病变支数较其他证候因素多,Gensini积分值由高至低分别是:寒凝>血瘀>阳虚>热蕴>阴虚>痰饮>气虚>气滞。从本虚角度考虑,随着气虚、阴虚、阳虚,病变程度逐渐加重。寒凝与血瘀在多支病变支数分布和Gensini积分值均较高,说明随着寒凝、血瘀的出现,冠脉病变范围和程度趋于严重.
4典则相关分析提示FIB与气虚、hs-CRP与痰饮、cTNI与寒凝有相关性。
5以进行二值Logistic回归分析气虚、阳虚、血瘀、痰浊的影响因素,发现吸烟年限和心衰病史为血瘀的影响因素;体重指数、西方饮食方式为痰饮的影响因素;高血压家族史、合并高血压病和心功能为阳虚的影响因素;劳累为气虚的影响因素)。
6对中青年男性和老年男性进行对照,发现中青年男性发病与吸烟、西方饮食方式有关,而老年男性与合并高血压病关系密切(P<0.05)。
7 ACS组TT基因型高于对照组,CC基因型低于对照组,差异有统计学意义,T等位基因频率在ACS组显著高于正常对照组(P<0.05)。实证组与对照组相比,在基因频率和等位基因分布两方面均有显著性差异(P=0.018;P=0.004)。实证组与虚证组相比及虚证组与对照组相比,在基因频率和等位基因分布两方面均没有显著性差异(P>0.05)。
8研究TT基因型和T等位基因发生急性冠脉综合征及其ACS实证或虚证的危险度。与对照组相比,ACS组TT基因型和T等位基因发生急性冠脉综合征的0R值大于1(P<0.05),说明TT基因型和T等位基因是ACS的易感基因。实证组与对照组相比0R值大子1(P<0.05),但实证组与虚证组、虚证组与对照组比较,P值均大于0.05,因此尚不能说明TT基因型和T等位基因与ACS实证组或虚证组相关。
结论
1 ACS证候因素为痰浊、血瘀、阳虚、气虚、气滞、寒凝、热蕴、阴虚。
2 ACS中医证候因素与冠状动脉造影病变支数分布和Gensini积分值有关。
3 FIB与气虚;hs-CRP与痰饮;cTNI与寒凝相关。
4吸烟年限和心衰病史为血瘀的影响因素;体重指数、西方饮食方式为痰饮的影响因素;高血压家族史、合并高血压病和心功能为阳虚的影响因素;劳累为气虚的影响因素。
5中青年男性发病与吸烟、西方饮食方式有关,而老年男性与合并高血压病关系密切。
6 GNB3基因C825T多态性T等位基因可能是ACS发病的遗传危险因素之一;未证实与ACS虚、实证候的明确相关性。
Objective
According to the methods and principles of clinical epidemiology,using modern statistical methods,his study probed into the TCM syndrome pattern of ACS sampling from Beijing of Han People.To investigate the relationship between the changes of coronary angiography(CAG),laboratory indices and the types of TCM syndromes,in order to present the basis in microcosmic determination of treatment based on differentiation of syndromes.To explore the relationship between the types of TCM syndromes and G-proteinβ3 submit(GNB3) C825T polymorphisms.
Methods
315 clinical cases diagnosed as ACS hospitaled in Anzhen hospital in Beijing of Han People.Using the factor analysis method,this study explored the types of syndrome.This study explored the realationship between the affection branches and the types of syndrome,compared the difference between Gensini accumulated points also.Using Canonical analysis method,this study investigated the relationship between the laboratory indices(TC、TG、LDL-C、hs-CRP、TNI、HCY、FIB)and the types of syndrome.The influencing factor was analyzed by using Binary-Logistic regresstion. The difference between male whose age＜60 and male whose age≥60 was compared. 103 health adults was enrolled as control group.The relationship between the types of TCM syndromes and GNB3 C825T polymorphisms was investigated.
Results
1.The number of TCM symtorns of ACS in the frenqency was as follows:chest distress,cardiopalmus,short breath,perspiration when chest pain,oral lips cyanosis, lack of power,pricking pain,anesthesia and heavy,waist soreness,loss of memory.
2.Using the factor analysis method,8 types of TCM syndromes were found.There was no significant statistical difference in the gender,age groups,clinical categorization of ACS over the distribution of TCM syndromes(P＞0.05).
3.There were correlations between the types of TCM syndromes and coronary arteriongraphy(P＜0.05).There was significant statistical difference in the number of coronary artery pathologic changes over the distribution of the 8 types of TCM syndromes(P=0.007).The grades of Gensini were different in the different types of TCM syndromes(P=0.001).The accumulation-syndrome of pathogenic cold was more than other syndromes in the number of coronary artery pathologic changes (P＜0.05).The sequence from the first to the last one by the grades of Gensini:the accumulation-syndrome of pathogenic cold＞the syndrome of blood stasis＞the deficiency-syndrome of yang＞heat＞the deficiency-syndrome of yin＞the syndrome of sputum-turbid＞the deficiency-syndrome of qi＞stagnation-syndrome of qi.While consider the deficiency-syndrome of essence,the degree of aeteria coronaria pathologic changes was more and more severious with the appearance of the deficiency-syndrome of qi,the deficiency-syndrome of yin,the deficiency-syndrome of yang.The accumulation-syndrome of pathogenic cold and the syndrome of blood stasis was the more serious than other syndromes,because their numbers of coronary artery pathologic changes and grades of Gensini were both high.
4.Canonical analysis showed that FIB was correlated with the deficiency-syndrome of qi;hs-CRP was correlated with the syndrome of sputum-turbid; cTNI was correlated with the accumulation-syndrome of pathogenic cold.
5.This study investigated the influential factors of such syndromes of ACS:the deficiency-syndrome of qi,the deficiency-syndrome of yang,the syndrome of blood stasis,the syndrome of sputum-turbid.The times of smoking and history of heart failurethe was influential factors of the syndrome of blood stasis.BMI and the western style of diet were the influencing factor of the syndrome of sputum-turbid.Family history of essential hypertension,essential hypertension and heart function were the influencing factor of the deficiency-syndrome of yang.Exertion was the influencing factor of the deficiency-syndrome of qi.
6.Comparing the male those age＜60 and male those age≥60,the male patients those age＜60 were correlated with cigarettes and western style of diet.While the male patients whose age≥60 were correlated with essential hypertension(P＜0.05).
7.The TT gene type of GNB3 was significantly higher in patients of ACS than control group,while CC gene type of GNB3 was significantly lower than control group and TT gene type was significantly higher than control group(P＜0.05).The frequence of T allele was higher than control group(P＜0.05).Comparing with control group, the sthenia syndrome had significant difference both in distribution and frequency of T allele.Those were no significant difference in frequency of TT genotype and T allele in compared the sthenia syndrome with the deficiency syndrome,and compared the deficiency syndrome with the control group(P＞0.05).
8.This study investigated the risk of the appearance of the sthenia syndrome and the deficiency syndrome due to TT genotype or T allele.Those carriers of the TT genotype and T allele of ACS were easier to become ACS than the control group(OR＞1,P＜0.05).TT genotype and T allele may be the predisposing genes to ACS.The value of OR in the sthenia syndrome was exceed 1 than the control group(P＜0.05). But comparing not only control group but also the sthenia syndrome,the value of P in the deficiency syndrome was larger than 0.5.For this reason,the TT genotype and T allele were not affirmed the association with the sthenia syndrome and deficiency syndrome of ACS.
Conclusion
1.The syndromes of ACS:the syndrome of sputum-turbid,the syndrome of blood stasis,the deficiency-syndrome of yang,the deficiency-syndrome of qi,the stagnation-syndrome of qi,the accumulation-syndrome of pathogenic cold,heat,the deficiency-syndrome of yin.
2.There were correlations between the types of TCM syndromes with coronary arteriongraphy.
3.FIB was correlated with the deficiency-syndrome of qi,hs-CRP was correlated with the syndrome of sputum-turbid,cTnI was correlated with the accumulation-syndrome of pathogenic cold.
4.The times of smoking and history of heart failurethe was influential factors of the syndrome of blood stasis.BMI and the western style of diet were the influencing factor of the syndrome of sputum-turbid.Family history of essential hypertension, essential hypertension and heart function were the influencing factor of the deficiency-syndrome of yang.Exertion was the influencing factor of the deficiency-syndrome of qi.
5.The male patients whose age＜60 were correlated with cigarettes and western style of diet.While the male patients whose age≥60 were correlated with essential hypertension.
6.The TT allele C825T of GNB3 gene may be one of the genetic risk factors of ACS.The TT genotype and T allele were not affirmed the association with the sthenia syndrome and deficiency syndrome of ACS.
引文
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