黑龙江省东部地区汉族人群PCSK9基因第8、9外显子多态性与冠心病的相关性

目的揭示前蛋白转化酶枯草溶菌素(PCSK)9基因第8、9外显子多态性突变位点与冠心病(CHD)的关系。方法选取经冠脉血管造影(CAG)确诊CHD者为CHD组共303例,非CHD者为对照组共233例。收集两组一般资料及临床资料,并记录入院后大生化数据(如血脂、血糖)。采用聚合酶链反应(PCR)对所提取的DNA基因组中PCSK9基因第8、9外显子扩增,测序,确定PCSK9第8、9外显子单核苷酸多态性(SNP)形式及突变频率,揭示其与低密度脂蛋白胆固醇(LDL-C)浓度的关系。结果在黑龙江省东部地区汉族人群中,未发现PCSK9基因第8外显子的突变位点,在第9外显子的筛查中共发现3个突变位点:c.477 T>C、c.604 C>T、c.606 C>T。对照组基因位点c.477 T>C突变患者血清LDL-C浓度水平与非突变者相比无明显变化(P>0.05)。CHD组基因位点c.604 C>T突变患者血清LDL-C浓度水平与非突变患者比较存在明显差异(P<0.05);基因位点c.606 C>T突变患者的血清LDL-C浓度水平与非突变患者相比无明显变化(P>0.05)。结论在黑龙江省东部地区汉族人群PCSK9基因第9外显子的c.604 C>T突变与CHD存在相关性。     

新疆维吾尔族PCSK9基因多态性与冠心病的相关性探讨

目的探讨新疆维吾尔族人类前蛋白转化酶枯草溶菌素9(PCSK9)基因E670G多态性位点与冠心病(CHD)的相关性。方法选择2013年1月—2014年12月在新疆医科大学第一附属医院冠心病科住院的CHD病人368例(维吾尔族176例,汉族192例)作为CHD组,同期在新疆医科大学第一附属医院体检的健康体检者372名(维吾尔族167名,汉族205名)作为对照组。应用聚合酶链反应测定E670G基因的多态性,并采用基因测序法验证。结果 1CHD组总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)水平显著高于健康对照组,高密度脂蛋白胆固醇(HDL-C)水平显著低于健康对照组,差异有统计学意义(P0.05)。2CHD组和对照组各基因型间三酰甘油(TG)、HDL-C水平比较差异无统计学意义;而CHD组和对照组AG基因型TC水平比较差异有统计学意义(P0.05),LDL-C水平差异有统计学意义(P0.05);CHD组AA基因型TC及LDL-C水平明显高于对照组AA基因型(P0.05),CHD组AG基因型TC及LDL-C水平明显高于对照组AG基因型,差异有统计学意义(P0.05)。3CHD组与对照组PCSK9基因的AG基因型及G等位基因频率增多,AA基因型减少,AA基因型、AG基因型及G等位基因分布差异有统计学意义(P0.05)。4新疆维吾尔族AG基因型及G等位基因频率均高于汉族,新疆维吾尔族AA基因型及A等位基因频率均低于汉族,两民族间基因型和等位基因频率分布差异有统计学意义(P0.05)。5新疆维吾尔族CHD组AG基因型、G等位基因频率均高于对照组,CHD组AA基因型及A等位基因频率均低于对照组,差异有统计学意义(P0.05)。结论 PCSK9基因E670G多态性位点主要以AA和AG基因型存在,CHD病人PCSK9基因E670G多态性与TC、LDL-C水平升高相关,新疆维、汉两民族E670G多态性存在差异,PCSK9基因E670G多态性对维吾尔族CHD的发生发展存在影响,G等位基因可能是维吾尔族CHD病人的危险因素。     

邯郸地区汉族人群酰基辅酶A:胆固醇酰基转移酶1位点rs1044925基因多态性与冠心病患者血脂代谢的相关性研究

目的探究酰基辅酶A:胆固醇酰基转移酶1(ACAT-1)位点1044925基因多态性与冠心病患者血脂代谢的相关性。方法选取2015年邯郸市第一医院心内一科收治的冠心病住院患者396例作为冠心病组,另选择同期冠状动脉造影检查正常者428例作为对照组。采用聚合酶链反应-限制性片段长度多态性分析法(PCR-RFLP)对两组患者ACAT-1位点rs1044925基因多态性进行分析。比较两组受试者体质指数(BMI)、血脂指标、ACAT-1位点rs1044925基因型及等位基因分布情况,分别比较两组不同基因型受试者血脂指标。结果冠心病组患者BMI及血清三酰甘油(TG)、总胆固醇(TC)、低密度脂蛋白胆固醇(LDL-C)、非高密度脂蛋白胆固醇(n HDL-C)、脂蛋白(a)水平均高于对照组,血清高密度脂蛋白胆固醇(HDL-C)水平低于对照组(P0.05);两组受试者血清载脂蛋白A_1(ApoA_1)、载脂蛋白B(Apo B)水平比较,差异无统计学意义(P0.05)。两组受试者基因型和A、C等位基因分布情况比较,差异均无统计学意义(P0.05)。对照组不同基因型受试者血清TC、TG、LDL-C、nHDL-C、LDL-C、ApoA_1、Apo B及脂蛋白(a)水平比较,差异均无统计学意义(P0.05)。冠心病组不同基因型患者血清TC、TG、nHDL-C、ApoA_1、Apo B及脂蛋白(a)水平比较,差异均无统计学意义(P0.05);AA基因型患者血清HDL-C水平低于AC/CC基因型患者,血清LDL-C水平高于AC/CC基因型患者(P0.05);采用协方差分析校正性别、年龄和BMI,结果显示冠心病组AA基因型患者血清HDL-C水平低于AC/CC基因型患者,血清LDL-C水平高于AC/CC基因型患者(P0.05)。结论邯郸地区汉族人群ACAT-1位点rs1044925基因多态性与冠心病患者血清LDL-C和HDL-C水平有关,ACAT-1位点rs1044925基因多态性可能通过影响血脂代谢而参与冠心病的发生和发展。     

早发冠心病患者脂蛋白脂酶基因多态性与血脂关系研究

目的:探讨早发冠心病(CHD)患者脂蛋白脂酶(LPL)基因多态性特征及其与血脂关系。方法:收集106例早发CHD患者(早发CHD组)血脂参数等资料,应用聚合酶链反应-限制性片段长度多态性方法,分析LPL的P、H基因型及其等位基因频率分布(HindⅢ和PVUⅡ酶切),并与81例非CHD者(对照组)进行比较。结果:早发CHD组血清胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)水平较对照组明显升高(P<0.05),高密度脂蛋白胆固醇(HDL-C)水平较对照组降低(P<0.05)。早发CHD组P+,H+等位基因频率高于对照组(P<0.05)。H+H+基因型TC、TG明显高于H+H-基因型,HDL-D低于H+H-基因型;P+P+基因型TG明显高于P-P-基因型,HDL-C低于P-P-基因型(均P<0.05)。结论:早发CHD患者血清TC、TG和LDL-C高于对照组,HDL-C低于对照组;P+,H+等位基因频率高于对照组。H+H+和P+P+基因型影响血脂水平。     

海南黎族人群载脂蛋白B基因XbaⅠ和EcoRⅠ位点的多态性及其对血脂和载脂蛋白的影响

目的研究我国海南地区黎族人群载脂蛋白B基因(apoB)XbaⅠ和EcoRⅠ位点的多态性及其对血脂及载脂蛋白的影响。方法采用聚合酶链反应(PCR)结合限制性片段长度多态性(RFLP)分析的方法,分析居住在海南黎族聚居村屯的无血缘关系的年龄在20～84岁之间的151名黎族居民和同地区200名汉族居民的apoB基因XbaⅠ和EcoRⅠ位点多态性,并测定其血清apoA、apoB、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDLC),并计算低密度脂蛋白胆固醇(LDL-C)、血清脂蛋白(a)。结果黎族人群组apoB基因的XbaⅠ位点X+等位基因频率高于汉族对照组(P<0.05);黎族人群组apoB基因EcoRⅠ位点的E-等位基因频率与汉族对照组比较没有差异(P>0.05)。黎族人群组的TC、LDL-C的水平低于汉族对照组,HDL-C的水平高于汉族对照组,而apoA、apoB、TG水平,两组间无差异。黎族人群组apoB基因XbaⅠ位点X+/X-基因型的LDL-C水平高于同组中的X-/X-基因型(P<0.05),而X+/X-基因型的HDL-C水平低于同组中的X-/X-基因型(P<0.05),apoA、apoB、TG、TC水平在两组间比较无差异(P>0.05)。黎族人群组apoB基因EcoRⅠ位点E+/E+基因型的TC、TG、HDL-C、LDL-C、apoA、apoB水平与同组的E+/E-基因型比较无差异(P>0.05)。结论黎族人群apoB基因XbaⅠ位点X+等位基因频率高于汉族人群,其具有种族特异性;黎族人群apoB基因EcoRⅠ位点E-等位基因频率与汉族人群无差异。黎族人群的X+等位基因能够影响海南黎族人群血脂代谢,E-等位基因不影响海南黎族人群血脂代谢。     

海南黎族人群载脂蛋白B基因XbaⅠ和EcoRⅠ位点的多态性及其对血脂和载脂蛋白的影响

目的研究我国海南地区黎族人群载脂蛋白B基因(apoB)XbaⅠ和EcoRⅠ位点的多态性及其对血脂及载脂蛋白的影响。方法采用聚合酶链反应(PCR)结合限制性片段长度多态性(RFLP)分析的方法,分析居住在海南黎族聚居村屯的无血缘关系的年龄在20～84岁之间的151名黎族居民和同地区200名汉族居民的apoB基因XbaⅠ和EcoRⅠ位点多态性,并测定其血清apoA、apoB、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDLC),并计算低密度脂蛋白胆固醇(LDL-C)、血清脂蛋白(a)。结果黎族人群组apoB基因的XbaⅠ位点X+等位基因频率高于汉族对照组(P<0.05);黎族人群组apoB基因EcoRⅠ位点的E-等位基因频率与汉族对照组比较没有差异(P>0.05)。黎族人群组的TC、LDL-C的水平低于汉族对照组,HDL-C的水平高于汉族对照组,而apoA、apoB、TG水平,两组间无差异。黎族人群组apoB基因XbaⅠ位点X+/X-基因型的LDL-C水平高于同组中的X-/X-基因型(P<0.05),而X+/X-基因型的HDL-C水平低于同组中的X-/X-基因型(P<0.05),apoA、apoB、TG、TC水平在两组间比较无差异(P>0.05)。黎族人群组apoB基因EcoRⅠ位点E+/E+基因型的TC、TG、HDL-C、LDL-C、apoA、apoB水平与同组的E+/E-基因型比较无差异(P>0.05)。结论黎族人群apoB基因XbaⅠ位点X+等位基因频率高于汉族人群,其具有种族特异性;黎族人群apoB基因EcoRⅠ位点E-等位基因频率与汉族人群无差异。黎族人群的X+等位基因能够影响海南黎族人群血脂代谢,E-等位基因不影响海南黎族人群血脂代谢。     

载脂蛋白B基因rs2070665位点多态性与肃南裕固族、汉族人群血脂水平的相关性研究

目的:探讨载脂蛋白B(ApoB)基因单核甘酸多态性rs2070665位点在甘肃裕固族、汉族人群中的分布及其与血脂水平的关系。方法:用高通量飞行质谱基因分型法(MALDI-TOF)分别对甘肃肃南裕固族227人和汉族306人进行ApoB基因rs2070665位点多态性检测和血脂水平检测,分析两者的相关性。结果:1裕固族血脂异常组总胆固醇(TC)和低密度脂蛋白胆固醇(LDL-C)水平明显高于汉族血脂异常组(P0.05)。2汉族TC和CC基因型分布频率明显高于裕固族(P0.01);裕固族血脂异常组TC基因型LDL-C值高于汉族(P0.05),裕固族血脂异常组CC基因型三酰甘油(TG)水平低于汉族(P0.05),裕固族健康对照组TT基因型TG水平明显高于汉族(P0.01);同民族内血脂异常组、健康对照组不同基因型血脂水平比较差异无统计学意义。3汉族T和C等位基因频率分布均高于裕固族(均P0.01);同民族对比,裕固族ApoB基因rs2070665位点C等位基因携带者患血脂异常的风险高于T等位基因携带者(OR:1.778;95%CI:1.136~2.780),汉族无差异。结论:甘肃肃南裕固族人群和汉族人群ApoB基因rs2070665位点基因多态性差异显著,裕固族人群ApoB基因rs2070665位点C等位基因携带者具有血脂异常遗传易感性。     

载脂蛋白H基因多态性与冠心病及血脂代谢关系的研究

目的探讨载脂蛋白H(ApoH)外显子3、8基因多态性与冠心病(CHD)、血脂代谢的关系。方法采用聚合酶链式反应-单链构象多态技术(PCR-SSCP)分析方法,分析了100例健康人及110例CHD患者的ApoH外显子3,8基因型及血脂测定。结果(1)CHD组外显3 GG基因型的频率为81.8%,GA+AA基因型频率为18.2%,G等位基因频率为88%,A等位基因频率是12%,与对照组比较无差异。(2)CHD组外显子8 GG基因型频率为74.5%,GC基因型频率为25.5%,G等位基因频率为87%,C等位基因频率为13%,与对照组比较CHD组的GC基因型频率及C等位基因频率显著增高。(3)外显子3 CHD组低密度胆固醇(LDL-C)高于对照组(P<0.05),CHD组及对照组各基因型间的血脂水平无差异;(4)外显子8 CHD组LDL-C也显著高于对照组(P<0.05),CHD组GC基因型的甘油三酯(TG)显著高于GG型和及对照组的各基因型。结论(1)ApoH外显子3基因多态性与CHD及血脂代谢无相关性;(2)ApoH外显子8 GC基因型及C等位基因与CHD有关,ApoH外显子8基因多态性与TG有关。     

β-羟甲基戊二酰辅酶A还原酶基因多态性与冠心病相关性的研究

目的研究汉族人群β-羟甲基戊二酰辅酶A还原酶(HMGCR)基因型和等位基因频率分布的遗传背景,探讨HMGCR多态性与冠心病的相关性。方法采用聚合酶链反应-单链构象多态性分析及测序技术,对湖北地区汉族123例健康人以及117例冠心病病人HMGCR多态性基因型和等位基因频率分布进行分析,研究HMGCR多态性对血脂、脂蛋白和载脂蛋白水平的影响。结果冠心病组内TT/CC(TT+CC)基因型与TT基因型相比,血清TC和LDL-C水平均有显著性差异(P<0·05)。冠心病组与对照组相比,2725A/G位点基因型间血脂、脂蛋白及载脂蛋白水平均无显著性差异(P>0·05)。结论HMGCR基因3089T/C位点基因多态性可能与冠心病存在相关性,而2725A/G位点多态性与血脂水平的相关性不明显。     

载脂蛋白E多态性与冠心病患者脂代谢的临床研究

目的研究载脂蛋白E(apoE)多态性与冠心病(CHD)及其脂代谢之间的关系。方法采用等电点聚焦电泳免疫印迹技术测定91例CHD及105例正常对照者的apoE表型,并用酶法测定他们的脂质水平。结果CHD组和对照组apoE表型分布及等位基因频率无显著性差异(P＞0．05)。CHD组不同apoE表型之间血脂水平比较发现,apoE基因多态性与胆固醇(TC)(P＜0．01)、低密度脂蛋白胆固醇(LDL-C)(P＜0．01)、甘油三酯(TG)(P＜0．05)有关,即E4等位基因携带者具有较高的TC和LDL-C水平,而E2等位基因携带者具有较低的TC和LDL-C水平。E2和E4等位基因携带者TG水平均升高。结论apoE基因多态性影响CHD患者的脂代谢,并通过影响脂代谢在CHD中起重要作用,但不是CHD的一个独立危险因素。     

E670G polymorphism of PCSK9 gene of patients with coronary heart disease among Han population in Hainan and three provinces in the northeast of China

Objective: To investigate the correlation between E670 G polymorphism of proprotein convertase subtilisin/kexin type 9(PCSK9) gene and coronary heart disease(CHD), and contrastively study the regional differences of E670 G polymorphism of PCSK9 gene between patients with CHD among the Han population in Hainan and three provinces in the northeast of China(TPNC), providing scientific basis for prevention and treatment of patients with CHD in different regions. Methods: A total of 233 cases of patients with CHD were selected from the Han population in Hainan and TPNC as the experimental group(118 cases from Hainan, 115 cases from TPNC), and 239 cases with non-CHD were selected among the Han population also in the two regions as control group(125 cases from Hainan, 114 cases from TPNC). The triglyceride(TG), total cholesterol(TC), high density lipoprotein cholesterol and low density lipoprotein cholesterol(LDL-C) levels of plasma were tested and PCR-RFLP method was used to test the E670 G polymorphism of PCSK9 gene. The statistical software package SPSS 21.0 was used for the statistical analysis and P0.05 was considered as statistically significant. Results: The levels of systolic pressure, diastolic blood pressure, fasting blood sugar, TC, TG, and LDL-C of patients in CHD group were significantly higher than those in non-CHD group, while the high density lipoprotein cholesterol level was lower than that in non-CHD group(P0.05). In CHD group, the frequencies of AG, GG genotypes of PCSK9 gene and G allele were higher than those in non-CHD group(P0.05), and in CHD group, the frequencies of AG, GG genotypes and G allele of patients both in Hainan and TPNC were higher than those in control group(P0.05). Among the patients with CHD, the frequencies of GG genotype and G allele of patients in Hainan were lower than those in TPNC(P0.05), and in CHD group, the levels of TG, TC and LDL-C of GG genotype were higher than those of AA genotype(P0.05). While in non-CHD group, there were no significant differences between the frequencies of GG genotype and G allele of patients in Hainan and TPNC(P0.05). Conclusions: There was a close correlation between the E670 G polymorphism of PCSK9 gene and CHD with serum lipid level. Among Han population in Hainan and TPNC, the E670 G polymorphism of PCSK9 gene of patients with CHD exhibited regional differences.     

Association between plasma levels of proprotein convertase subtilisin/kexin type 9 (PCSK9) and lipids with rs7903146 polymorphisms of the TCF7L2 gene in diabetic patients

The rs7903146 polymorphism of TCF7L2 gene is known as the strongest genetic risk factor for type 2 diabetes mellitus (T2DM). The polymorphism is in association with clinical profile of T2DM patients. PCSK9 is a serine protease that promotes LDLR degradation and regulates circulating levels of lipids. The association of this polymorphism with PCSK9 and metabolic profile of diabetic and healthy subjects was investigated. This cross-sectional study was performed on 132 T2DM patients and the same number of healthy subjects. All the participants were genotyped for the rs7903146 single nucleotide polymorphism by the PCR-RFLP method. Metabolic profile including plasma levels of PCSK9, triglycerides, total cholesterol, non-HDL cholesterol, LDL cholesterol, HDL cholesterol, fasting plasma glucose, and HBA1C was measured. PCSK9, total cholesterol, and LDL-C levels were lower in the diabetic patients as compared to the healthy subjects. There were also direct and significant associations between PCSK9 and TG, TC, LDL-C, and non HDL-C in the subjects. Values of plasma glucose, HbA1c, PCSK9, TC, and LDL-C were higher in patients with TT genotype, but the differences were not statistically significant for all. A positive Spearman correlation was found between PCSK9 levels and the genotypes in all the participants. The results confirm the association of rs7903146 in the TCF7L2 gene with metabolic parameters and PCSK9. The T allele was associated with higher lipid and PCSK9 levels.

     

小肠型脂肪酸结合蛋白基因多态性与老年冠心病人群发病风险的研究

目的研究老年人群小肠型脂肪酸结合蛋白(I-FABP)基因编码区外显子2中第54位密码子多态性与冠心病患者血脂水平和冠心病发病风险的关系。方法随机选取老年冠心病患者56例作为病例组,同时选取我院体检中心的健康老年人49例作为对照组,记录一般临床资料,检测TC、TG、LDL-C、HDL-C水平,同时采用聚合酶链反应技术、DNA限制性内切酶酶切技术检测该人群的I-FABP基因HhaⅠ酶切位点的多态性。结果所有受试者I-FABP基因编码区外显子第54位密码子存在HhaⅠ酶切位点,产生多态性片段为野生型A/A、杂合突变型A/T、纯合突变型T/T。病例组A/T、T/T基因携带者TC、TG、LDL-C水平明显高于A/A携带者,差异有统计学意义(P<0.05)。对照组A/A基因携带者与A/T、T/T基因携带者TC、TG、LDL-C、HDL-C差异无统计学意义(P>0.05)。体质量指数、饮食习惯、I-FABP等位基因是冠心病主要的独立危险因素。结论样本人群中存在I-FABP基因多态性;I-FABP基因多态性影响老年冠心病患者的脂质代谢水平,与老年人冠心病发病风险有关,可能是冠心病发生的遗传易感因素。     

Additive effect of mutations in LDLR and PCSK9 genes on the phenotype of familial hypercholesterolemia

Patients homozygous or compound heterozygous for LDLR mutations or double heterozygous for LDLR and apo B R3500Q mutation have higher LDL-C levels, more extensive xanthomatosis and more severe premature coronary disease (pCAD) than simple heterozygotes for mutations in either these genes or for missense mutations in PCSK9 gene. It is not known whether combined mutations in LDLR and PKCS9 are associated with such a severe phenotype. We sequenced Apo B and PCSK9 genes in two patients with the clinical diagnosis of homozygous FH who were heterozygous for LDLR gene mutations. Proband Z.P. (LDL-C 13.39 mmol/L and pCAD) was heterozygous for an LDLR mutation (p.E228K) inherited from her father (LDL-C 8.07 mmol/L) and a PCSK9 mutation (p.R496W) from her mother (LDL-C 5.58 mmol/L). Proband L.R. and her sister (LDL-C 11.51 and 10.47 mmol/L, xanthomatosis and carotid atherosclerosis) were heterozygous for an LDLR mutation (p.Y419X) inherited from their mother (LDL-C 6.54 mmol/L) and a PCSK9 mutation (p.N425S) probably from their deceased father. The LDL-C levels in double heterozygotes of these two families were 56 and 44% higher than those found in simple heterozygotes for the two LDLR mutations, respectively. The two PCSK9 mutations are novel and were not found in 110 controls and 80 patients with co-dominant hypercholesterolemia. These observations indicate that rare missense mutations of PCSK9 may worsen the clinical phenotype of patients carrying LDLR mutations.     

Chronic kidney disease on hemodialysis is associated with decreased serum PCSK9 levels

Objectives

Serum low density lipoprotein-cholesterol (LDL-C) correlates positively with serum PCSK9 in the general population, consistent with PCSK9 being a determinant of LDL-C levels. Patients with chronic kidney disease (CKD) on hemodialysis (HD) have lower total cholesterol (TC) and LDL-C compared to the general population. Serum PCSK9 and its relationship with serum lipids have not been reported in CKD patients on HD (CKD-HD).

Methods

We measured serum PCSK9 by ELISA and lipid levels in 66 CKD-HD patients and compared them to 178 non-CKD subjects. Since statins increase serum PCSK9 levels, CKD-HD patients were separated into those not on statin therapy (HD-NS, n = 32) and those taking statins (HD-S, n = 34). No control subjects were on statin therapy.

Results

Serum PCSK9, TC, LDL-C and HDL-C levels were significantly lower in the CKD-HD group (n = 66) compared to the control group. HD-NS patients showed lower PCSK9, TC and LDL-C levels than control subjects and PCSK9 levels correlated with TC and LDL-C levels (r = 0.35, p = 0.050; r = 0.423, p = 0.0158 respectively) as well as TG levels (r = 0.413, p = 0.0188). In HD-S patients, PCSK9 levels were not significantly different from the non-CKD group. There was no correlation between PCSK9 levels and TC and LDL-C levels in the HD-S group.

Conclusion

Our data are the first quantitative analysis of serum PCSK9 levels in CKD-HD patients. We show that serum PCSK9 in HD-NS patients is decreased and it retains a positive correlation with LDL-C, suggesting that PCSK9 may remain a significant determinant of LDL-C in CKD-HD subjects. We also show that statin therapy disrupts the correlation between LDL-C and PCSK9 in CKD-HD patients. These data suggest that the regulation of LDL-C by PCSK9 remains intact in CKD-HD patients. PCSK9 may also play a role in the metabolism of triglyceride-rich lipoproteins in CKD-HD patients.     

Interactions of the LIPG 584C>T polymorphism and alcoholconsumption on serum lipid levels

Both endothelial lipase gene(LIPG)584C>T (rs2000813)polymorphism and alcohol consumption modulate serum lipid levels.But their interactions on serum lipid profiles are not well known.The present study was undertaken to detect the interactions of LIPG 584C>T polymorphism and alcohol consumption on serum lipid levels.Genotyping of the LIPG 584C>T was performed in 763 nondrinkers and 520 drinkers aged 15-85.Interactions between the genotypes and alcohol consumption were assessed by using a cross-product term.The levels of serum total cholesterol(TC),triglyceride (TG),high-density lipoprotein cholesterol(HDL-C),apolipoprotein (Apo) AI,and the ratio of ApoAI to ApoB were higher in drinkers than in nondrinkers(P<0.01 for all).There was no significant difference in the genotypic and allelic frequencies between nondrinkers and drinkers.The levels of serum TC, HDL-C and ApoAI in nondrinkers were different among the three genotypes(P<.05-.01).The subjects with CT genotype had higher serum TC,HDL-C and ApoAI levels than the subjects with CC genotype.The levels of serum HDL-C and ApoAI in drinkers were different among the three genotypes (P<.001 and P<.05;respectively).The individuals with TT genotype had higher serum HDL-C and ApoAI levels than the individuals with CC and CT genotypes.The levels of TC in nondrinkers were correlated with LIPG 584C>T allele (P<.05),whereas the levels of TG and HDL-C were associated with LIPG 584C>T alleles(P<.05) and genotypes (P<.05);respectively.The present study suggests that the subjects with TT genotype benefited more from alcohol consumption than the subjects with CT and TT genotypes in increasing serum HDL-C and ApoAI levels.     

Interactions of the apolipoprotein C-Ⅲ3238C>G polymorphism and alcohol consumption on serum triglyceride levels

Objectives Both apolipoprotein(Apo)C-Ⅲgene polymorphism and alcohol consumption have been associated with increased serum triglyceride(TG) levels,but their interactions on serum TG levels are not well known.The present study was undertaken to detect the interactions of the ApoC-Ⅲ3238C>G(rs5128) polymorphism and alcohol consumption on serum TG levels.Methods A total of 516 unrelated nondrinkers and 514 drinkers aged 15-89 were randomly selected from our previous stratified randomized cluster samples. Genotyping of the ApoC-Ⅲ3238C>G was performed by polymerase chain reaction and restriction fragment length polymorphism combined with gel electrophoresis,and then confirmed by direct sequencing.Interactions of the ApoC-Ⅲ3238C>G genotype and alcohol consumption was assessed by using a cross-product term between genotypes and the afore-mentioned factor.Results Serum total cholesterol(TC), TG,high-density lipoprotein cholesterol(HDL-C),ApoA-I and ApoB levels were higher in drinkers than in nondrinkers (P<0.05-0.001).There was no significant difference in the genotypic and allelic frequencies between the two groups. Serum TG levels in nondrinkers were higher in CG genotype than in CC genotype(P<0,01).Serum TC,TG,low-density lipoprotein cholesterol(LDL-C) and ApoB levels in drinkers were higher in GG genotype than in CC or CG genotype(P<0.01 for all).Serum HDL-C levels in drinkers were higher in CG genotype than in CC genotype(P<0.01).Serum TC, TG,HDL-C and ApoA-I levels in CC genotype,TC,HDL-C, ApoA-I levels and the ratio of ApoA-I to ApoB in CG genotype, and TC,TG,LDL-C,ApoA-I and ApoB levels in GG genotype were higher in drinkers than in nondrinkers(P<0.05-0.01).But the ratio of ApoA-I to ApoB in GG genotype was lower in drinkers than in nondrinkers(P<0.01). Multivariate logistic regression analysis showed that the levels of TC,TG and ApoB were correlated with genotype in non drinkers(P<0.05 for all).The levels of TC,LDL-C and ApoB were associated with genotype in drinkers(P<0.0     

KIF6基因rs20455多态性与中国北方汉族人冠心病及血脂水平的关联研究

目的分析KIF6基因rs20455多态性与中国北方汉族人群冠心病及血脂水平的关系。方法收集164例冠心病(CHD)患者及152例健康人的外周血标本;应用聚合酶链反应-限制性片段长度多态性技术检测KIF6 rs20455多态性;研究基因多态性对血糖、血脂水平的可能影响。结果中国北方汉族人KIF6基因rs20455多态性位点TT、TC、CC基因型频率分别为0.291,0.491与0.218;T等位基因,C等位基因频率分别为0.536与0.464。基因型和等位基因频率在组间分布差异均无统计学意义(P>0.05)。本研究对象rs20455多态性基因型和等位基因频率分布与高加索,非裔美洲人群有统计学差异(P<0.001)。rs20455基因多态性与血糖、血脂水平、性别、年龄、高血压病史无显著性关联。Logistic回归显示,年龄、TG、HbAlc是本组研究对象发生冠心病的主要危险因素(OR分别为1.178、26.18、17.415,P<0.05)。C等位基因不是发生冠心病的独立危险因素。结论未发现KIF6基因rs20455多态性与本研究人群的冠心病发生及血脂水平存在明显关联性。