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载脂蛋白A5基因多态性与中国汉族人群冠心病患者血脂及冠脉狭窄程度相关性研究

发布时间:2018-07-17 03:42
【摘要】:目的:探讨载脂蛋白A5(APOA5)基因rs662799、rs2075291和rs3135507多态性位点与中国汉族人群冠状动脉粥样硬化性心脏病(CHD)患者血脂水平及冠状动脉狭窄程度的关系。方法:选择川北医学院附属医院2014年4月至2015年7月间,临床疑似诊断为CHD并行冠状动脉造影的住院患者,并根据造影结果,将至少一支主要冠脉分支的管腔狭窄程度在50%以上者诊断为CHD,作为CHD组;正常冠状动脉者、冠状动脉粥样硬化症者和轻度冠状动脉狭窄(狭窄率小于50%)归为非CHD对照组。应用聚合酶链式反应-限制性片段长度多态性法(PCR-RFLP)对所有纳入者进行rs2075291、rs3135507和rs662799多态性分型。通过生理生化检查,获得高血压、糖尿病、体重指数(BMI)、甘油三酯(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、高密度脂蛋白胆固醇(HDL-C)、载脂蛋白B100(APOB100)和载脂蛋白AI(APOAI)等临床资料,并计算TG/HDL-C、TC/HDL-C、LDL-C/HDL-C和APOB100/APOAI等比值指标。采用Gensini评分法评价CHD患者的冠脉狭窄程度,并比较不同基因型之间血脂水平及冠状狭窄程度的差异。结果:1.纳入rs2075291和rs3135507多态性分型的476例受试者中,经冠状动脉造影术确诊为CHD的患者324例,其中男性204例,平均年龄(64.74±9.42)岁;女性120例,平均年龄(64.55±8.31)岁。非CHD对照者152例,其中男性81例,平均年龄(60.12±12.41)岁;女性71例,平均年龄(59.30±9.68)岁。chd组高血压患病率、tg、tc、apob100、tg/hdl-c、tc/hdl-c、ldl-c/hdl-c和apob100/apoai水平高于对照组,hdl-c和apoai水平低于对照组,差异均有统计学意义(p0.05)。两组人群中apoa5rs2075291多态性位点基因型均以gg型多见,其次为gt型,成功分型的受试者中未检测到tt型纯合子;其等位基因频率分布均以g等位基因为主要等位基因,c等位基因为次要等位基因。chd及非chd组中,apoa5rs3135507多态性位点基因型以gg型多见,其次为ga型,aa型较少见,g等位基因频率均显著高于a等位基因。rs2075291和rs3135507多态性等位基因及基因型分布频率在chd组与对照组之间差异无统计学意义。在对照组中,rs2075291多态性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,差异均有统计学意义(p0.05);在chd组中,rs2075291多态性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,差异均有统计学意义(p0.05)。在对照组及chd组中,rs3135507多态性不同基因型之间血脂水平差异无统计学意义。在chd组中,gensini得分在rs2075291和rs3135507多态性基因型之间差异无统计学意义。2.在进行rs662799多态性分型的478例受试者中,chd的患者325例,其中男性205例,平均年龄(64.63±9.51)岁;女性120例,平均年龄(64.48±8.30)岁。非chd对照者153例,其中男性81例,平均年龄(59.88±12.58)岁;女性72例,平均年龄(59.14±9.69)岁。两组人群中apoa5rs662799多态性位点基因型均以tt型多见,其次为tc型,cc型较少见。其等位基因频率分布均以t等位基因为主要等位基因,C等位基因为次要等位基因。女性对照组中次要等位基因C携带者血清TG/HDL-C水平明显高于TT型纯合子,HDL-C水平显著低于TT基因型个体,差异均有统计学意义(P0.05);CHD患者中,男性群体C等位基因携带者血清TG、TG/HDL-C水平高于TT基因型参试者,女性群体C等位基因携带者血清TG、TG/HDL-C、TC/HDL-C、APOB/APOAI水平高于TT基因型参试者,差异均有统计学意义(P0.05)。女性群体脂代谢紊乱组rs662799多态性CC、TC基因型分布、C等位基因频率高于正常组,差异均有统计学意义(P0.05)。在女性CHD患者中,C等位基因携带者频率以及C等位基因频率随Gensini评分增加而逐级增加(P0.05)。多元线性回归分析显示,在校正了高血压、TC、LDL-C、APOAI水平等冠心病潜在危险因素之后,女性CHD患者中rs662799基因多态性与Gensini评分独立显著相关(Beta=0.157,95CI:0.017-0.298,P=0.028)。结论:在我国汉族人群中,APOA5 rs2075291位点与血浆TG升高、HDL-C降低相关联,但与CHD发病风险及CHD患者冠脉狭窄程度没有明显相关性;APOA5 rs3135507位点与血浆脂质水平及CHD均无显著相关性。女性中APOA5 rs662799多态性显著影响血脂水平,并且与CHD冠状动脉狭窄程度相关。
[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.
【学位授予单位】:川北医学院
【学位级别】:硕士
【学位授予年份】:2017
【分类号】:R541.4

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