中国人内源性高甘油三酯血症与载脂蛋白A5基因-1131T>C多态性、S19W多态性的相关性

目的探讨中国人内源性高甘油三酯血症患者载脂蛋白A5基因的-1131T〉C多态性及S19W多态性与血脂水平的关系。方法用聚合酶链反应-限制性片断长度多态性分析，对182名内源性高甘油三酯血症患者和200名血脂正常者的载脂蛋白A5基因启动子上游-1131T〉C单核苷酸多态性、编码区的S19W（c．56C〉G）多态性、空腹血脂及载脂蛋白水平进行分析。结果患者的体质指数、血清总甘油三酯和总胆固醇水平较对照组显著升高，高密度脂蛋白胆固醇水平则显著降低。-1131T／C单核苷酸多态性位点T和C等位基因频率在病例组和对照组分别为52．7％、47．3％和67.0％、33．0％。等位基因频率和基因型频率分布符合Hardy-Weinberg平衡定律。T/C基因多态性等位基因T和C频率在两组问的差异有显著性（P〈0．05）；S19W多态性与内源性高甘油三酯血症发病风险未见明显相关性。结论载脂蛋白A5基因-1131C等位基因与血清甘油三酯的升高相关。     

国人载脂蛋白E基因多态性与冠心病发病之间的相关性

目的 探讨载脂蛋白E基因112bp与158bp位点多态性与血脂水平及冠心病发生之间的关系。方法采用生物化学法分别测量经冠状动脉造影证实的89例冠心病患者及43例正常人空腹血脂水平，应用聚合酶链反应限制片长多态性分析方法对载脂蛋白E基因DNA244bp的5’末端片段进行限制性片段长度多态性分析。结果冠心病组甘油三酯、总胆固醇、低密度脂蛋白、载脂蛋白B及脂蛋白（a）水平均高于对照组（P〈0．05），而载脂蛋白A1水平则低于对照组（P〈0、05）；冠心病组载脂蛋白Eε2基因型频率明显为低（P〈0．001）。结论载脂蛋白E基因多态性特征会明显影响人群中个体的血浆脂质水平，从而增加人群中个体发生冠心病的危险。     

CD14基因-159C／T位点多态性对哮喘患者血浆IL-5的影响

目的探讨CD14基因-159C／T位点多态性和支气管哮喘（哮喘）的相关性及其对血浆IL-5的影响。方法选择正常对照组和哮喘组各150例,取外周血离心后,用酶联免疫吸附试验法测定血浆IL-5,用限制性片段长度多态性-聚合酶链反应方法检测CD14基因-159C／T位点多态性分布。结果对照组和哮喘组等位基因C、T分布有统计学差异（Х^2=10．82,P〈0．01）,C等位基因与哮喘相关（C／T的OR=1．73,95％CI=1．25—2．39,P〈0．01）,两组基因型（TT、CT、CO）频率分布有统计学差异（r=9．73,P〈0．01）;同组内C等位基因携带者血浆IL-5高于非携带者,以CC基因型最高;同一基因型哮喘组IL-5高于对照组。结论CD14基因启动子-159位点多态性与哮喘相关,C等位基因与血浆IL-5升高相关。     

有冠心病家族史儿童载脂蛋白E基因多态性的研究

目的：探讨有冠心病（CHD）家族史儿童载脂蛋白（apo)E基因多态性的分布及其对血脂、脂蛋白、apo的影响。方法：采用改良的聚合酶链式反应－限制性片段长度多态性方法,分析83例有CHD家族史的儿童和282例无CHD家族史的儿童apoE基因型。结果：与无CHD家族史的儿童比较,有CHD家族史儿童apoε4等位基因频率较高（分别为6．0％、15．7％,P＜0．01）。早发CHD家族史的儿童ε4等位基因频率较非早发及无CHD家族史儿童为高,三组之间的ε4等位基因频率差异有性（分别为18．3％、14．8％、6．0％,P＜0．05。apoE基因多态性对有CHD家族史儿童的血脂水平有影响,ε2、ε3、ε4等位基因携带有的血总胆固醇（TC）、低密度脂蛋白－胆固醇（LDL－C）、脂蛋白（a)、apoB100、apoE浓度有差异（P＜0．05）;与ε3等位基因携带比较,ε4具有较高的血TC、LDL－C、apoB100水平和较低的apoAⅠ、apoE水平;ε2等位基因携带的血TC、LDL－C和脂蛋白（a)水平较低（P＜0．05）。结论有CHD家族史儿童apoE基因多态性其他儿童不同,并对血浆脂蛋白代谢产生明显影响。     

纤维蛋白原Bβ链-148C/T基因多态性及血小板膜糖蛋白VIT13254C基因多态性与冠心病的关系

目的 探讨纤维蛋白原（Fib）Bβ链-148C／T基因多态性及血小板膜糖蛋白Ⅵ（GpⅥ）T13254C基因多态性在血栓形成中的作用及其与冠心病的关系。方法 采用Clauss法测定154例经选择性冠状动脉造影检查，确诊为冠心病的患者及121例经冠状动脉造影证实无冠脉病变的对照者血浆Fib水平，以多聚酶链式反应-限制性内切酶片段长度多态性（PCR-RFLP）分析血小板膜糖蛋白基因多态性及纤维蛋白原Bβ链-148C／T基因多态性。结果 急性心肌梗死组（AMI组）和不稳定心绞痛组（UAP组）血浆Fib水平均明显高于对照组（P〈0．001），AMI组血浆Fib水平较UAP组明显增高（P〈0．001）；三组间FibBβ-148C／T的基因型和等位基因频率分布无显著性差异（分别为x^2=1．78，P〉0．05;x^2=0．567，P〉0．05）；急性心肌梗死患者中，两组基因型间血浆Fib水平具有显著差异（P〈0．05）。GpⅥ T13254C的C等位基因频率为0．033；冠心病组与对照组GpⅥ T13254C的基因型和等位基因频率分布无显著性差异（分别为x^2=0．617，P〉0．05；x^2=0．148，P〉0．05）。结论 Fib是冠心病的一个独立危险因素，FibBⅥ-148C／T基因多态性与AMI组血浆Fib水平明显相关，与冠心病的发生无直接关系。本地人群的GpⅥ T13254C等位基因频率明显低于外国人，其基因多态性与冠心病的发生无显著相关。     

整合素-α2基因多态性与脑梗死发病的关系及其对脂代谢的影响

目的探讨整合素-α2（ITGA2）基因C807T多态性与脑梗死发病的关系及其对脂代谢的影响,研究急性脑梗死的发病机制。方法应用聚合酶链反应—限制性片段长度多态性（PCR-RFLP）方法检测脑梗死组及正常对照组的ITGA2基因型;同时按常规方法测定血浆脂质、脂蛋白水平。结果 ITGA2基因C807T多态性两组比较有统计学差异（P〈0.05）,T等位基因携带者患脑梗死的风险是C等位基因的1.635倍（OR=1.635,95%C：I 1.232－2.171）,携带T等位基因脑梗死患者的血清TC水平明显高于不携带者（P〈0.05）。结论 ITGA2基因C807T多态性与脑梗死发病有相关性,T等位基因可能是其发病的遗传易感基因;携带T等位基因的个体可能通过影响血脂水平而增加脑梗死的发病风险。     

冠心病患者载脂蛋白A5和载脂蛋白C3基因多态性的研究

目的研究中国北方汉族人群中载脂蛋白A5基因(APOA5)-1131F／C、56C／G多态性和载脂蛋白C3基因(APOC3)-482C／T多态性与冠心病的关系。方法采用聚合酶链反应．限制性片段长度多态性(PCR-RFLP)结合聚丙烯酰胺凝胶电泳(PAGE)技术检测了312例经冠状动脉造影确诊的冠心病患和317例健康对照APOA5-1131T／C、56C／G和APOC3-482C／T多态性基因型和等位基因的分布,同时采用生化方法检测了研究对象的血脂水平。结果冠心病组APOA5-1131C等位基因频率明显高于对照组(39．9％比33．3％,P=0．02)。CC纯合子患冠心病的风险是TT纯合子的1.93倍(95％CI：1．12～3．32),且通过Logistie回归分析发现该相关性独立于性别、年龄、体重指数、吸烟史、高血压糖尿病患病史及血清TC、HDK-C、IDL-C水平;冠心病组CC纯合子的TG水平明显高于TC杂合子,而TT纯合子TG水平最低。虽然APOA5-1131T／C和APOC3—482C／T多态性存在连锁不平衡,但前的作用与后无关。结论APOA5-1131T／C基因多态性对人群血清TG水平有影响,APOA5-1131C等位基因可能与我国北方汉族人冠心病的发生相关联。     

载脂蛋白E基因多态性对血脂及高血压病的影响

为探讨载脂蛋白E基因多态性对血脂及高血压病的影响，采用聚合酶链式反应－限制性片段多态性方法测定112例原发性高血压病人及118例非高血压病对照的载脂蛋白E基因型。结果发现高血压病患者ε4等位基因频率及载脂蛋白E ε4携带者显著高于对照组（P＜0．05）。载脂蛋白E ε4携带者的总胆固醇和低密度脂蛋白胆固醇水平显著高于载脂蛋白E ε2携带者（P＜0．05），载脂蛋白E ε3／ε3携带者的低密度脂蛋白胆固醇水平也显著高于载脂蛋白E ε2携带者（P＜0．05）。载脂蛋白E ε4携带是高血压病的独立危险因素（P＜0．05）。研究表明载脂蛋白E基因多态性影响个体的血脂和脂蛋白水平，载脂蛋白E ε4为高血压病的一种重要遗传标志。     

C反应蛋白及其基因多态性与冠心病发病的相关性研究

采用全自动生化分析仪测定188例冠心病患者（冠心病组）和98例健康查体者（对照组）的血清C反应蛋白（CRP）水平，同时应用聚合酶链反应检测CRP的1059O／C基因多态性，结合冠状动脉造影结果进行分析。结果冠心病组的自然对数转换CRP（InCRP）水平显著高于对照组，Logistic回归分析显示InCRP水平（0R：1．44，P〈0．01）与冠心病独立相关，1059G／C基因多态性等位基因和基因型的分布频率符合Hardy-Weinberg平衡（χ^2=0.297，P〉0.05），两组1059G／C基因型和等位基因的分布趋势相同，差异无显著性；C等位基因携带者的InCRP水平低于GG基因型（P=0．024），而冠状动脉病变程度不受1059G／C基因多态性的影响（妒=1．374，P〉0．05）。认为血清CRP水平升高可能是冠心病的独立危险因子,CRP水平可能受其1059G／C基因多态性的影响。     

载脂蛋白C-Ⅲ基因多态性与早发冠心病的关系

目的探讨载脂蛋白C—Ⅲ（ApoC—Ⅲ）C-482T基因多态性与早发冠心病的关系。方法172例男性小于55岁，女性小于65岁，行冠状动脉造影检查的患者，按冠脉造影的结果分为早发冠心病纽（病例组）及非早发冠心病组（对照组）。用聚合酶链反应-限制性片段长度多态性方激PCR—RFLP）检测所有研究对象ApoC-Ⅲ基因型。结果病例组与对照组基因型频率比较无显著性差异，x^2=0．394，P=0．821；C、T等位基因频率比较无显著性差异，x^2=0．168，P=0．682。结论ApoC-ⅢC-482T基因型和等位基因频率分布在早发冠心病组和对照组中无差异，不能认为ApoC—ⅢC-482T是早发冠心病的易感基因。     

Genetic determinants of the response to bezafibrate treatment in the lower extremity arterial disease event reduction (LEADER) trial

Genetic determinants of baseline levels and the fall in plasma triglyceride and fibrinogen levels in response to bezafibrate treatment were examined in 853 men taking part in the lower extremity arterial disease event reduction (LEADER) trial. Three polymorphisms in the peroxisome proliferator activated receptor alpha (PPARalpha) gene were investigated (L162V, G>A in intron 2 and G>C in intron 7), two in the apolipoprotein CIII (APOC3) gene (-482C>T and -455T>C) and one in the beta-fibrinogen (FIBB) gene (-455G>A). The presence of diabetes (n=158) was associated with 15% higher triglyceride levels at baseline compared to non-diabetics (n=654) (P<0.05). Among the diabetic group, carriers of the PPARalpha intron 7 C allele had 20% lower triglyceride levels compared to homozygotes for the common G allele (P<0.05), with a similar (non-significant) trend for the L162V polymorphism, which is in linkage disequilibrium with the intron 7 polymorphism. For the APOC3 gene, carriers of the -482T allele had 13% lower baseline triglyceride levels compared to -482C homozygotes (P<0.02), but no effect was observed with the -455T>C substitution. In the non-diabetic patients, the PPARalpha V162 allele was significantly associated with 9% higher baseline triglyceride levels (P<0.03) and a similar, but non-significant trend was seen for the intron 7 polymorphism. Overall, triglyceride levels fell by 26% with 3 months of bezafibrate treatment, and current smokers showed a poorer response compared to ex/non-smokers (23% fall compared to 28% P=0.03), but none of the genotypes examined had a significant influence on the magnitude of response. Carriers of the -455A polymorphism of the FIBB gene had, as expected, marginally higher baseline fibrinogen levels, 3.43 versus 3.36 g/l (P=0.055), but this polymorphism did not affect response to treatment. Overall, fibrinogen levels fell by 12%, with patients with the highest baseline fibrinogen levels showing the greatest decrease in response to bezafibrate. For both the intron 2 and the L162V polymorphisms of the PPARalpha gene there was a significant interaction (both P<0.01) between genotype and baseline levels of fibrinogen on the response of fibrinogen levels to bezafibrate, such that individuals carrying the rare alleles in the lowest tertile showed essentially no overall decrease compared to a 0.18 g/l fall in homozygotes for the common allele. Thus while these genotypes are a minor determinant of baseline triglyceride and fibrinogen levels, there is little evidence from this study that the magnitude of response to bezafibrate treatment in men with peripheral vascular disease is determined by variation at these loci.     

Contribution of apolipoprotein C-III gene variants to determination of triglyceride levels and interaction with smoking in middle-aged men

Variation within and around the apolipoprotein C-III (APOC3) gene has been associated with elevated triglyceride (Tg) levels and cardiovascular disease. The associations of 4 polymorphic variants in the APOC3 gene (3238C>G in the 3' untranslated region [SST:I], 1100C>T in exon 3, -482C>T in the insulin-responsive element, and -2854T>G in the APOC3-A4 intergenic region) with plasma Tg and cholesterol levels and their interaction with smoking have been investigated in the Second Northwick Park Heart Study (NPHSII), a large cohort of healthy men (n=2745). Analyzing the variants separately showed that 3238G, 1100T, and -482T alleles were all associated with raised Tg levels. For the 3238C>G and -482C>T sites, the Tg-raising effect appeared to depend on smoking status (test for interaction, P:=0.042 and P:=0.009, respectively), but for the 1100C>T site, the effect was constant irrespective of smoking status (test for interaction, P:=0.27). The -2854T>G site was not associated with effects on Tg levels in this sample. Because all of the variants showed significant allelic association, regression modeling was used to quantify the relative size of each effect and to assess whether the effects of the separate variants were independent. The 1100C>T variant had an independent effect on Tg levels that was not influenced by smoking status (increase of 8.2% in Tg with each T1100 allele), whereas the -482C>T variant had a separate effect that was dependent on smoking (increase of 13.7% in Tg for each -482T allele in current smokers, 8.6% in exsmokers, and -7.4% in those who never smoked). The 3238C>G variant did not show a separate independent effect on Tg concentration. Thus, by use of the regression model, it was possible to estimate how mean Tg levels would vary in groups of individuals with respect to APOC3 genotype and smoking information. Analysis in this large group of healthy men has allowed the identification of a statistically robust APOC3 genotype-smoking interaction, which now warrants further molecular study.     

Polymorphisms in the insulin response element of APOC-III gene promoter influence the correlation between insulin and triglycerides or triglyceride-rich lipoproteins in humans.

OBJECTIVE: To assess whether the -455 and -482 mutations in APOC-III gene insulin response element affect the relationships between plasma insulin and triglyceride-rich lipoprotein levels. DESIGN: Population-based studies. SUBJECTS: The population sample was composed of 983 subjects (485 men and 498 women), aged between 35 and 65 y, randomly sampled from the electoral rolls in Northern France and stratified on gender and 10 y age groups. MEASUREMENTS: Plasma triglyceride, apolipoprotein C-III, apoB, LpC-III:B and LpE:B lipoprotein particles and insulin levels were measured. Two polymorphisms in APOC-III gene insulin response element (T-->C at -455 and/or C-->T at -482) were determined. RESULTS: Plasma insulin was positively correlated to triglyceride levels (P<0.0001), apo C-III (P<0.003), LpC-III:B (P<0.0001), apoB (P<0.0001) and LpE:B (P<0.0001). This association differed significantly according to APOC-III insulin response element polymorphisms. The relationship between insulin and LpC-III:B (P<0.02) or apoB (P<0.02) was greater in women bearing the C allele of -455 than the T allele. Similarly, the relationship between insulin and LpC-III:B (P<0.02) or LpE:B (P<0.05) was greater in women bearing the T allele of -482 than the C allele. There was no evidence for any effect in men. CONCLUSION: These results suggest that the relationship between plasma insulin and triglyceride-rich lipoprotein levels is partly influenced by polymorphisms in APOC-III insulin response element.     

动脉硬化性脑梗死患者载脂蛋白A5基因多态性研究

目的研究载脂蛋白A5基因-1131T>C多态性位点各基因型及等位基因分布频率及其与动脉硬化性脑梗死(arteriosclerotic cerebral infarction,ACI)的关系。方法选择221例湖北地区汉族人群(对照组)及90例ACI患者(ACI组),应用聚合酶链反应限制性片段长度多态性对每个个体的基因型进行鉴定。同时,采用酶法和免疫比浊法对研究对象血脂进行检测。结果2组间除性别、年龄、体重指数无显著差异外,其他各项指标(吸烟、收缩压、舒张压、胆固醇、高密度脂蛋白胆固醇、低密度脂蛋白胆固醇、载脂蛋白A1及载脂蛋白B)均有显著差异(P<0.05);ACI组稀有等位基因C携带者甘油三酯水平明显高于C非携带者,2组中TT、TC、CC 3种基因型甘油三酯水平差异有显著性意义(P<0.05);ACI组稀有等位基因C的频率明显高于对照组(χ2=5.568,P=0.018)。结论apoA5-1131C等位基因与ACI患者甘油三酯水平升高有关,其不同基因型及等位基因在湖北汉族人群及ACI患者中的分布不同,可能与该地区人群ACI危险性有关。     

Pleiotropic effects of TCF7L2 gene variants and its modulation in the metabolic syndrome: from the LIPGENE study

Aims/hypothesisVariants of the TCF7L2 gene predict the development of type 2 diabetes mellitus (T2DM). We investigated the associations between gene variants of TCF7L2 and clinical features of the metabolic syndrome (MetS) (an entity often preceeding T2DM), and their interaction with non-genetic factors, including plasma saturated fatty acids (SFA) concentration and insulin resistance (IR).MethodsFasting lipid profiles, insulin sensitivity, insulin secretion, anthropometrics, blood pressure and 10 gene variations of the TCF7L2 gene were determined in 450 subjects with MetS.ResultsSeveral single nucleotide polymorphisms (SNP) showed phenotypic associations independent of SFA or IR. Carriers of the rare T allele of rs7903146, and of three other SNPs in linkage disequilibrium with rs7903146, had lower blood pressure and insulin secretion. High IR and the presence of the T-allele of rs7903146 acted synergistically to define those with reduced insulin secretion. Carriers of the minor allele of rs290481 exhibited an altered lipid profile, with increased plasma levels of apolipoprotein B, non-esterified fatty acids, cholesterol and apolipoprotein B in triglyceride rich lipoproteins, and LDL cholesterol. Carriers of the minor allele of rs11196224 that had higher plasma SFA levels showed elevated procoagulant/proinflammatory biomarkers, impaired insulin secretion and increased IR, whereas carriers of the minor allele of rs17685538 with high plasma SFA levels exhibited higher blood pressure.Conclusions/interpretationSNP in the TCF7L2 gene are associated with differences in insulin secretion, blood pressure, blood lipids and coagulation in MetS patients, and may be modulated by SFA in plasma or IR.     

Polymorphisms in the fatty acid-binding protein 2 and apolipoprotein C-III genes are associated with the metabolic syndrome and dyslipidemia in a South Indian population

The Chennai Urban Population Study investigates a South Indian population with a high prevalence of cardiovascular disease associated with the metabolic syndrome (MS). The Ala54Thr polymorphism in the fatty acid-binding protein 2 (FABP2) gene as well as the T-455C and C-482T polymorphisms in the apolipoprotein C-III (APOC3) gene promoter have been associated with features of the MS in specific populations. This study evaluates in Asian-Indians the association between these polymorphisms with MS and dyslipidemia, defined according to National Cholesterol Education Program Adult Treatment Panel III. Allelic frequencies in 70 controls and 110 patients with diabetes from the Chennai Urban Population Study were 52.9% for FABP2 Thr54, 73.0% for APOC3 -482T, and 80.2% for APOC3 -455C. The polymorphisms were in agreement with Hardy-Weinberg equilibrium. Controls carrying FABP2 Thr54 were more likely to have MS than noncarriers (Fisher's exact test P = 0.031; odds ratio = 6.9 with a 95% confidence interval of 1.1, 43.9). Those carrying at least one polymorphic allele in both genes had a higher likelihood of having MS than wild type (Fisher's exact test P = 0.003; odds ratio = 12.1 with a 95% confidence interval of 1.88, 77.6). Dyslipidemia was associated with the polymorphism as well. The polymorphisms were not associated with MS in patients with diabetes. The association of the polymorphisms with MS and dyslipidemia could contribute to the high cardiovascular disease prevalence in this population.     

Association of two apolipoprotein A-I gene MspI polymorphisms with high density lipoprotein (HDL)-cholesterol levels and indices of obesity in selected healthy Chinese subjects and in patients with early-onset type 2 diabetes

OBJECTIVE: Previous studies have reported associations between two apolipoprotein A-I (apoA-I) gene MspI polymorphisms (G-75A and C83T) and high density lipoprotein (HDL)-cholesterol and/or apoA-I levels, but have not investigated the relationship with obesity. METHODS: We determined the distribution of these polymorphisms in 482 early-onset (< or = 40 years) Type 2 Chinese diabetics and 167 Chinese selected healthy controls. RESULTS: The -75A and 83T allele frequencies were similar in the diabetic and healthy subjects. In the healthy control subjects, HDL-cholesterol levels were significantly higher in the AA homozygotes than in the GG/GA carriers (1.74 +/- 0.58 vs. 1.45 +/- 0.58 mmol/l, P<0.001). Furthermore, analyses showed a significant relationship between increasing HDL-cholesterol tertiles and the AA genotype frequency in the selected healthy subjects (3.6, 8.9 and 16.1%, P=0.026). For the C83T polymorphism, healthy male CT carriers had higher HDL-cholesterol levels than CC homozygotes (1.71 +/- 0.57 vs. 1.25 +/- 0.30 mmol/l, P=0.001), but this was not found in females. No relationship between these polymorphisms and lipid levels was found in the diabetics, who had a more adverse lipid profile than the selected controls. In the diabetics, but not the controls, in CT carriers compared to CC homozygotes there were lower levels of body mass index (BMI; 23.8 +/- 3.9 vs. 25.4 +/- 4.7 kg/m2, P=0.048) and waist-to-height ratio (0.49 +/- 0.06 vs. 0.52 +/- 0.07, P=0.023), and this relationship was supported by tertile analysis. CONCLUSIONS: The -75AA genotype was associated with higher HDL-cholesterol levels in the selected healthy, but not diabetic, subjects. The 83T allele was associated with greater indices of obesity in the diabetic patients, and with higher HDL-cholesterol in heterozygous healthy male subjects.     

Genetic influences on blood pressure within the Stanislas Cohort

OBJECTIVE: To investigate the association of 21 polymorphisms within 13 genes, APOE, APOB, APOC3, CETP, LPL, PON1, MTHFR, FGB, F5, GPIIIa, SELE, ACE and AGT, with inter-individual blood pressure (BP) variation. PARTICIPANTS: Seven hundred and seventy-six men and 836 women, free of antihypertensive and lipid-lowering medications, were selected from the Stanislas Cohort. RESULTS: ANOVA on blood pressure values after adjustment for covariates [age, body mass index (BMI), contraceptive pill, tobacco and alcohol] showed that lipoprotein lipase (LPL) Ser447Ter and glycoprotein IIIA (GpIIIa) Pl polymorphisms were significantly associated with BP in women (0.01 < or = P < or = 0.05), whereas BP levels in men were significantly different according to apolipoprotein CIII (APOC3) 3206T/G and -482C/T polymorphisms (P < or = 0.05). In women, compared to the most common allele, the GpIIIa Pl allele was associated with increased mean arterial pressure (MAP) (P < 0.05) and pulse pressure (PP) (P < 0.001), and the LPL 447Ter allele was associated with decreased systolic blood pressure (SBP) and PP levels (0.001 < or = P < or = 0.05). These two polymorphisms appeared to act independently. In men, the APOC3 3206GG genotype was related to decreased diastolic blood pressure (DBP) and MAP levels (P < or = 0.01), and the APOC3 -482T allele with decreased PP levels (P < or = 0.05). The presence of both the -482C allele and the 3206GG genotype was related to decreased DBP, suggesting that specific haplotypes might be involved. CONCLUSION: The APOC3, LPL and GpIIIa genes were found to be associated with BP levels. The contributions of these genes, although modest, are consistent with the polygenic nature of BP levels.     

An interaction between apo C-III variants and protease inhibitors contributes to high triglyceride/low HDL levels in treated HIV patients.

BACKGROUND: Long-term therapy with protease inhibitors (PI) is associated with hypertriglyceridaemia, low high-density lipoprotein (HDL) levels and accumulation of apolipoprotein (apo) E- and apo C-III-containing lipoproteins. OBJECTIVES: To evaluate the impact, on this dyslipaemic phenotype, of three polymorphisms of the apo C-III gene: two on an insulin response element and one in the 3'-region. Apo E genotypes were evaluated also. DESIGN: Sixty consecutive male patients attending the HIV follow-up consultation were included during a 3-month period. All patients received at least one PI. Apo C-III and apo E genotypes were determined. Besides routine bio-clinical examination, a detailed exploration of lipoproteins and of insulin secretion markers was carried out. METHODS: Plasma lipoparticles, insulin, proinsulin and C-peptide were measured by specific immuno-assays. Determination of apo C-III genotypes (-455C/T, -482C/T and SstI) and of apo E alleles (epsilon2, epsilon3 and epsilon4) were performed by amplification and endonuclease digestion and were confirmed by allele-specific oligonucleotide hybridization. RESULTS: Distribution of apo C-III alleles defined four major haplotypes. Carriers of the -455C variant had 30% lower levels of HDL-cholesterol than non-carriers. Plasma triglycerides increased according to the number of variant alleles. In multivariate analysis, a model including age, body mass index, clinical stage and treatment length, plasma insulin and apo C-III haplotypes explained around 43% of the HDL-cholesterol and triglycerides variability. Measurements of lipids before and after the use of PI demonstrated synergistic effects of the treatment and apo C-III variants on triglyceride levels. CONCLUSIONS: Apo C-III polymorphisms might identify a genetic predisposition to develop dyslipidaemia under PI therapy.     

Association between DNA variant sites in the apolipoprotein A5 gene and coronary heart disease in Chinese

The recently discovered apolipoprotein A5 ( APOA5 ) gene has been shown to be important in determining plasma triglyceride levels, a major cardiovascular disease risk factor. We searched for possible associations of the APOA5 gene polymorphisms S19W and -1131T>C with coronary heart disease (CHD) in a Chinese population. A total of 483 Chinese CHD patients and 502 control non-CHD subjects were genotyped by polymerase chain reaction-restriction fragment length polymorphism for these 2 single nucleotide polymorphisms. We found that the minor allele 19W was observed only in CHD patients and not in controls, with allelic frequencies of 0.047 and 0.000, respectively ( P < .000001), and the minor allele -1131C was significantly higher in CHD patients than in controls (0.391 vs 0.299, P < .0001). These results suggest that both the S19W and -1131T>C variations in the APOA5 gene are associated with the CHD and appear to be 2 genetic risk factors for CHD susceptibility in Chinese. Moreover, we found that triglyceride levels were significantly higher in -1131C carriers than in -1131T subjects of the control group and that high-density-lipoprotein cholesterol was decreased in -1131C carriers among CHD patients.