【摘要】：目的:探討載脂蛋白A5(APOA5)基因rs662799、rs2075291和rs3135507多態(tài)性位點與中國漢族人群冠狀動脈粥樣硬化性心臟病(CHD)患者血脂水平及冠狀動脈狹窄程度的關(guān)系。方法:選擇川北醫(yī)學院附屬醫(yī)院2014年4月至2015年7月間,臨床疑似診斷為CHD并行冠狀動脈造影的住院患者,并根據(jù)造影結(jié)果,將至少一支主要冠脈分支的管腔狹窄程度在50%以上者診斷為CHD,作為CHD組;正常冠狀動脈者、冠狀動脈粥樣硬化癥者和輕度冠狀動脈狹窄(狹窄率小于50%)歸為非CHD對照組。應用聚合酶鏈式反應-限制性片段長度多態(tài)性法(PCR-RFLP)對所有納入者進行rs2075291、rs3135507和rs662799多態(tài)性分型。通過生理生化檢查,獲得高血壓、糖尿病、體重指數(shù)(BMI)、甘油三酯(TG)、總膽固醇(TC)、低密度脂蛋白膽固醇(LDL-C)、高密度脂蛋白膽固醇(HDL-C)、載脂蛋白B100(APOB100)和載脂蛋白AI(APOAI)等臨床資料,并計算TG/HDL-C、TC/HDL-C、LDL-C/HDL-C和APOB100/APOAI等比值指標。采用Gensini評分法評價CHD患者的冠脈狹窄程度,并比較不同基因型之間血脂水平及冠狀狹窄程度的差異。結(jié)果:1.納入rs2075291和rs3135507多態(tài)性分型的476例受試者中,經(jīng)冠狀動脈造影術(shù)確診為CHD的患者324例,其中男性204例,平均年齡(64.74±9.42)歲;女性120例,平均年齡(64.55±8.31)歲。非CHD對照者152例,其中男性81例,平均年齡(60.12±12.41)歲;女性71例,平均年齡(59.30±9.68)歲。chd組高血壓患病率、tg、tc、apob100、tg/hdl-c、tc/hdl-c、ldl-c/hdl-c和apob100/apoai水平高于對照組,hdl-c和apoai水平低于對照組,差異均有統(tǒng)計學意義(p0.05)。兩組人群中apoa5rs2075291多態(tài)性位點基因型均以gg型多見,其次為gt型,成功分型的受試者中未檢測到tt型純合子;其等位基因頻率分布均以g等位基因為主要等位基因,c等位基因為次要等位基因。chd及非chd組中,apoa5rs3135507多態(tài)性位點基因型以gg型多見,其次為ga型,aa型較少見,g等位基因頻率均顯著高于a等位基因。rs2075291和rs3135507多態(tài)性等位基因及基因型分布頻率在chd組與對照組之間差異無統(tǒng)計學意義。在對照組中,rs2075291多態(tài)性gt基因型tg、tg/hdl-c和tc/hdl-c水平高于gg基因型,hdl-c和apoai水平低于gg基因型,差異均有統(tǒng)計學意義(p0.05);在chd組中,rs2075291多態(tài)性gt基因型tg、tg/hdl-c和tc/hdl-c高于gg基因型,hdl-c低于gg基因型,差異均有統(tǒng)計學意義(p0.05)。在對照組及chd組中,rs3135507多態(tài)性不同基因型之間血脂水平差異無統(tǒng)計學意義。在chd組中,gensini得分在rs2075291和rs3135507多態(tài)性基因型之間差異無統(tǒng)計學意義。2.在進行rs662799多態(tài)性分型的478例受試者中,chd的患者325例,其中男性205例,平均年齡(64.63±9.51)歲;女性120例,平均年齡(64.48±8.30)歲。非chd對照者153例,其中男性81例,平均年齡(59.88±12.58)歲;女性72例,平均年齡(59.14±9.69)歲。兩組人群中apoa5rs662799多態(tài)性位點基因型均以tt型多見,其次為tc型,cc型較少見。其等位基因頻率分布均以t等位基因為主要等位基因,C等位基因為次要等位基因。女性對照組中次要等位基因C攜帶者血清TG/HDL-C水平明顯高于TT型純合子,HDL-C水平顯著低于TT基因型個體,差異均有統(tǒng)計學意義(P0.05);CHD患者中,男性群體C等位基因攜帶者血清TG、TG/HDL-C水平高于TT基因型參試者,女性群體C等位基因攜帶者血清TG、TG/HDL-C、TC/HDL-C、APOB/APOAI水平高于TT基因型參試者,差異均有統(tǒng)計學意義(P0.05)。女性群體脂代謝紊亂組rs662799多態(tài)性CC、TC基因型分布、C等位基因頻率高于正常組,差異均有統(tǒng)計學意義(P0.05)。在女性CHD患者中,C等位基因攜帶者頻率以及C等位基因頻率隨Gensini評分增加而逐級增加(P0.05)。多元線性回歸分析顯示,在校正了高血壓、TC、LDL-C、APOAI水平等冠心病潛在危險因素之后,女性CHD患者中rs662799基因多態(tài)性與Gensini評分獨立顯著相關(guān)(Beta=0.157,95CI:0.017-0.298,P=0.028)。結(jié)論:在我國漢族人群中,APOA5 rs2075291位點與血漿TG升高、HDL-C降低相關(guān)聯(lián),但與CHD發(fā)病風險及CHD患者冠脈狹窄程度沒有明顯相關(guān)性;APOA5 rs3135507位點與血漿脂質(zhì)水平及CHD均無顯著相關(guān)性。女性中APOA5 rs662799多態(tài)性顯著影響血脂水平,并且與CHD冠狀動脈狹窄程度相關(guān)。
[Abstract]:Objective: To investigate the relationship between the apolipoprotein A5 (APOA5) gene rs662799, rs2075291 and rs3135507 polymorphism sites and the degree of coronary artery stenosis in patients with coronary atherosclerotic heart disease (CHD) in Chinese Han population. Methods: selected Affiliated Hospital of Chuanbei Medical College from April 2014 to July 2015, the clinical suspected diagnosis was CHD and Patients who were hospitalized with coronary angiography were diagnosed with at least one of the main coronary branches of at least 50% of the main coronary artery stenosis to CHD, as group CHD; normal coronary arteries, coronary atherosclerotic and mild coronary stenosis (less than 50%) were classified as non CHD controls. Polymerase chain reaction was used. Rs2075291, rs3135507, and rs662799 polymorphisms of all the participants were typed by the strain restriction fragment length polymorphism (PCR-RFLP) method. Hypertension, diabetes, body mass index (BMI), triglyceride (TG), total cholesterol (TC), low density lipoprotein cholesterol (LDL-C), high density lipoprotein cholesterol (HDL-C), and fat loaded eggs were obtained by physiological and biochemical tests. Clinical data such as white B100 (APOB100) and apolipoprotein AI (APOAI), and the ratio of TG/HDL-C, TC/HDL-C, LDL-C/HDL-C, and APOB100/APOAI were calculated. The degree of coronary stenosis in CHD patients was evaluated by Gensini score, and the difference of blood lipid level and coronal narrowing between different genotypes was compared. Results: 1. included rs2075291 and rs3135507. Among the 476 subjects of state classification, 324 patients were diagnosed with CHD by coronary angiography, of which 204 were male, the average age was (64.74 + 9.42) years, and 120 cases were female, the average age was (64.55 + 8.31) years old. The average age was 81, the average age (60.12 + 12.41) years, female 71, and the average age of.Chd group was high blood. TG, TC, apoB100, tg/hdl-c, tc/hdl-c, ldl-c/hdl-c and apob100/apoai were higher than those in the control group, and the levels of HDL-C and apoAI were lower than those in the control group (P0.05). The genotype of apoa5rs2075291 polymorphic loci in the two groups were all similar to GG type. The allele frequency distribution of the allele is G allele because of the main allele, and the C allele is secondary allele.Chd and non CHD group. The apoa5rs3135507 polymorphism loci are common in GG type, followed by GA type, and the AA type is rare, and the frequency of G allele is higher than that of.Rs2075291 and rs3135507 polymorphism of a allele. There was no significant difference in the distribution frequency between the CHD group and the control group. In the control group, the rs2075291 polymorphic GT genotype TG, tg/hdl-c and tc/hdl-c levels were higher than the GG genotypes, and the levels of HDL-C and apoAI were lower than the GG genotypes, and the differences were statistically significant (P0.05). C/hdl-c was higher than GG genotype, and HDL-C was lower than GG genotype, the difference was statistically significant (P0.05). There was no significant difference in the level of blood lipid between the rs3135507 polymorphism and the control group and the CHD group. In CHD group, there was no significant difference in Gensini score between rs2075291 and rs3135507 polymorphism genotypes. 799 of the 478 cases of polymorphic typing, 325 cases were CHD, of which 205 were male, average age (64.63 + 9.51), women 120, average age (64.48 + 8.30) years old and 153 non CHD controls, among them, 81, average age (59.88 + 12.58) years, female 72, average age (apoa5rs662799) age. The loci genotypes were all TT type, followed by TC type, and the CC type was rare. The allele frequency distribution of the allele was T allele because of the main allele, and the C allele was secondary allele. The serum TG/HDL-C level of the secondary allele C carriers in the female control group was significantly higher than that of the TT homozygote, and the HDL-C level was significantly lower than the TT genotype individual. The difference was statistically significant (P0.05); in the CHD patients, the C allele carriers of the male group were TG, the TG/HDL-C level was higher than those of the TT genotypes, and the serum TG, TG/HDL-C, TC/HDL-C, APOB/APOAI levels of the C allele carriers in the female population were higher than those of the TT genotypes. The differences were statistically significant. Group rs662799 polymorphism CC, TC genotype distribution and C allele frequency were higher than normal group, the difference was statistically significant (P0.05). In female CHD patients, the frequency of C allele carriers and the frequency of C allele increased with the Gensini score (P0.05). Multivariate linear regression analysis showed that hypertension, TC, LDL-C, were corrected. After the potential risk factors of coronary heart disease, the rs662799 gene polymorphism in female CHD patients was significantly correlated with Gensini score (Beta=0.157,95CI:0.017-0.298, P=0.028). Conclusion: in Chinese Han population, the APOA5 rs2075291 locus is associated with the increase of plasma TG and the decrease of HDL-C, but it is associated with the risk of CHD and the degree of coronary stenosis in CHD patients. No significant correlation was found; there was no significant correlation between APOA5 rs3135507 loci and plasma lipid levels and CHD. APOA5 rs662799 polymorphism in women significantly affected blood lipid levels, and was associated with the degree of coronary stenosis in CHD.
【學位授予單位】：川北醫(yī)學院
【學位級別】：碩士
【學位授予年份】：2017
【分類號】：R541.4

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