E-选择素A561C(S128R)基因多态性对动态血压的影响

目的:研究E-选择素A561C基因多态性对动态血压的影响。方法:原发性高血压组347例,对照组315例。2组年龄、体质指数(BMI)无显著性差异。对2组进行诊室血压测量,抽血检验生化指标。PCR-RFLP方法进行DNA多态性分析,电泳判断基因型并测序。结果:检测到AA、AC、CC三种基因型。在高血压组与非高血压组之间,基因型构成比有显著性差异(P<0·05)。在高血压组AC-CC基因型和C等位基因频率(6·92%和4·76%)显著高于对照组(分别为3·17%,2·22%),P值分别为0·029和0·013。C等位基因发生高血压的风险性是A等位基因的2·197倍[OR(OddsRatio)=2·197,95%可信区间为1·164~4·144]。同时AC-CC基因型的24h、白天、夜间血压以及血压最大值、最小值、血压负荷均大于AA基因型,其中夜间舒张期血压和舒张期血压负荷的P值分别是0·043和0·016,具有统计学意义。而且AC-CC基因型发生收缩压非勺型高血压的危险是AA的4·367倍。OR=4·367,95%可信区间:0·047~1·122。发生舒张压非勺型高血压的危险是AA的1·972倍。OR=1·972,95%可信区间:0·124~2·070。结论:E-选择素A561C基因多态性对高血压有显著影响,AC_CC基因型和C等位基因发生高血压风险较大,动态血压各血压指标较高,且更易发生血压节律异常。     

176例脑卒中患者E-选择素第四外显子A561C基因多态性分析

目的探讨E-选择素第四外显子A561C基因（以下简称A561C基因）多态性与辽西地区脑卒中的关系。方法选择辽西地区176例脑卒中患者（观察组）和152例健康体检者（对照组）,采用PCR-RFLP技术检测两组A561C基因的基因型。结果观察组及对照组AA型分别为152例（86.4%）、142例（93.4%）,AC型分别为24例（13.6%）、10例（6.6%）,两组比较P均〈0.05;观察组及对照组A型基因频率分别为328例（93.2%）、289例（96.7%）,C型分别为24例（6.8%）、10例（3.3%）,两组比较P均〈0.05。结论 A561C基因多态性与脑卒中的发病具有相关性,C等位基因可能是辽西地区人群脑卒中发病的遗传易感基因。     

抵抗素基因+299G/A多态性与T2DM并高血压病的相关性

目的研究抵抗素基因＋299G／A多态性与中国北方地区汉族人群2型糖尿病（T2DM）并高血压病的关系。方法采用聚合酶链式反应-限制性片段长度多态性技术检测北方地区汉族人群261例T2DM患者的抵抗素基因内含子2区299G／A突变。结果T2DM组GG、GA、AA基因型及G／A等位基因频率与非T2DM组比较有显著统计学差异（P〈0．01）；T2DM组GG基因型携带者空腹血糖明显高于AA基因型携带者（P〈0．05）。多元线性逐步回归分析显示，抵抗素基因＋299G／A与收缩压、舒张压无明显相关性。结论抵抗素基因＋299G／A多态性与T2DM有关．与高血压病元明显相关性。     

E-选择素基因多态性及血清可溶性水平与慢性HBV感染临床结局的关系

目的: 探讨E-选择素(E-selectin)基因第2号外显子G98T和第4号外显子A561C多态性及血清可溶性水平与慢性HBV感染临床结局之间的关系.方法: 从外周血中提取基因组DNA,采用聚合酶链反应-限制性片段长度多态性技术(PCRRFLP)检测367例慢性HBV感染者(其中慢性HBV携带者97例,慢性乙肝101例,肝硬化121例,肝癌48例)和281例健康对照者E-选择素基因G98T和A561C位点多态性,同时采用酶联免疫吸附实验(ELISA)检测各组可溶性E-选择素(sE-选择素)水平.结果: E-选择素A561C多态性中A/C+C/C基因型和C等位基因频率在肝硬化组与对照组相比差异有统计学意义( P = 0.006,0.002).A/C+C/C基因型患肝硬化的风险是AA基因型的2.45倍( OR = 2.45,95%CI: 1.28-4.72).E-选择素G98T多态性中各基因型频率和等位基因频率在各病例组与对照组相比差异无统计学意义,但在肝硬化患者中,Child-pugh B+C级与A级相比较,G/T+T/T基因型频率差异有统计学意义( P = 0.034),G/T+T/T基因型发展到Child-pugh B或C的风险是GG型的3.07倍( OR = 3.07,95%CI: 1.05-8.97).慢性乙肝组和肝硬化组血清sE-选择素水平明显高于对照组( P＜0.01);在肝硬化组中,血清sE-选择素水平从Child-pugh A级到C级明显降低( P＜0.05);在各组中,C等位基因携带者血清sE-选择素水平明显高于A等位基因携带者( P＜0.05).结论: E-选择素A561C基因多态性可能与慢性HBV感染后肝硬化的发生相关,并参与调控血清可溶性E-选择素的表达;E-选择素G98T基因多态性与慢性HBV感染后的临床结局无相关性,但可能与肝硬化的严重程度相关.     

E选择素A561C基因多态性与老年人心肌梗死和血脂的相关分析

目的 探讨中国湖北武汉地区E选择素基因A561C多态性与老年人心肌梗死的相关性，并对其与血脂、脂蛋白水平的关系进行分析。方法 应用聚合酶链反应和限制性片段长度多态性(PCR-RFLP)技术检测198例老年心肌梗死患者、187例中青年心肌梗死患者和190例老年健康对照者、185例中青年健康对照者E-选择素基因型，并按常规方法测定血脂水平。结果 E-选择素等位基因A、C频率在老年心肌梗死组和中青年心肌梗死组分别为：92．9％、7．1％和93．3％、6．7％；在老年健康对照组和中青年健康对照组分别为96．6％、3．4％和96.8％、3．2％，同龄梗死组与非梗死组间比较，差异有显著性(P＜0．05)。基因型频率分布符合Hardy-weinberg平衡定律。老年、中青年心肌梗死组分别与老年、中青年健康对照组比较，其基因型频率差异有显著性(均P＜0．05)；老年、中青年心肌梗死组血浆总胆固醇(TC)、甘油三酯(TG)和低密度脂蛋白胆固醇(LDL-C)均高于老年、中青年健康对照组(P＜0．05)。结论 E-选择素A561C基因多态性与老年心肌梗死的发病有关，C等位基因可能是心肌梗死发病的危险因素之一。     

乙醛脱氢酶2基因 rs671多态性和新疆汉族人群原发性高血压的关联性研究

目的：探讨乙醛脱氢酶2（ALDH2）基因 rs671多态性在新疆地区汉族人群原发性高血压（EH）发病中的作用。方法应用 Taqman 技术检测了474例汉族 EH 患者和358例正常血压者 ALDH2基因 rs671多态性。结果在男性人群中,饮酒组 rs671的 GA ＋AA 基因型频率和 A 等位基因频率均明显低于不饮酒组（P ＜0．01）;EH 组 rs671的 GA ＋AA 基因型频率和 A 等位基因频率均明显低于对照组（P ＜0．01）。而在女性人群中,EH 组和对照组 rs671的 3 种基因型频率和等位基因频率的分布差异无统计学意义（P ＞0．05）。非条件 Logistic 回归分析校正年龄、体重指数、糖尿病史、饮酒史等影响因素后,在男性人群中 rs671的 GA ＋AA 基因型者患 EH 的风险低于 GG基因型者（OR ＝0．656,95％CI：0．448～0．962,P ＜0．05）,GA ＋AA 基因型者收缩压水平明显低于GG 型者（P ＜0．05）。而在男性不饮酒者和女性人群中,GA ＋AA 基因型者和 GG 基因型者血压水平比较差异无统计学意义。结论ALDH2基因 rs671多态性可能和新疆汉族男性人群 EH 的发生相关,rs671的 GA ＋AA 基因型可能是汉族男性人群 EH 的一个保护因素。     

血管紧张素Ⅱ1型受体基因A1166/C多态性与冠心病病变程度的相关性研究

目的探讨血管紧张素Ⅱ1型受体（AT1R）基因A1166／（2多态性与冠心病（CHD）及其病变程度的关系、方法应用多聚酶链反应-限制性片段长度多态性（PCR—RELP）检测法，测定109例冠心病病人及106例对照者的AT1R基因型。结果冠心病组与对照组AA、AC基因型频率和等位基因频率A、C比较均无统计学意义（P〉0．05）；从冠状动脉病变积分和受累血管数两方面分析冠心病病变程度与基因变异的关系，AA、AC基因型和A、C等位基因频率在不同病变程度间也无统计学意义（P〉0．05）。结论AT1R基因A1166／C多态性与冠心病及其病变程度可能无关联.     

内皮素-2基因多态性与老年原发性高血压发生及非洛地平降压作用的关系

目的探讨内皮素-2基因多态性与老年原发性高血压及降压治疗效果的关系。方法汉族老年原发性高血压患者200例作为高血压组,健康体检老年人200例作为对照组。高血压患者给予非洛地平(5 mg,1次/d)口服治疗2个月。采用基因芯片技术测定内皮素-2基因A985G位点基因型。结果高血压组和对照组内皮素-2基因A985G位点基因型比较差异有统计学意义(P0.05),高血压组GG基因型高于对照组(P0.05),AA基因型和AG基因型低于对照组(P0.05)。高血压组和对照组内皮素-2基因A985G位点等位基因频率比较差异有统计学意义(P0.05),高血压组G等位基因频率高于对照组,A等位基因频率低于对照组(P0.05)。高血压组高血压家族史比例高于对照组(P0.05),体重指数、总胆固醇和三酰甘油水平均高于对照组(P0.05)。高血压患者治疗后收缩压和舒张压均明显低于治疗前(P0.05),GG基因型收缩压和舒张压下降值高于AA基因型和AG基因型(P0.05),AG基因型收缩压和舒张压下降值高于AA基因型(P0.05)。结论内皮素-2基因A985G位点基因多态性和老年原发性高血压的发病有关,应用非洛地平降压治疗后,GG基因型的降压效果更好。     

120例类风湿性关节炎患者Ghrelin基因C408A多态性观察

目的 探讨Ghrelin基因C408A多态性与类风湿性关节炎（RA）的关系。方法 采用PCR-RFLP方法结合DNA测序技术检测120例RA患者（观察组）和150例健康查体者（对照组）Ghrelin基因C408A位点多态性及等位基因频率分布情况。结果 Ghrelin基因C408A位点存在碱基二态性C或A。对照组基因型CC型107例（71.3%）、CA型41例（27.3%）、AA型2例（1.4%）,观察组CC型71例（59.2%）、CA型46例（38.3%）、AA型3（2.5%）;对照组等位基因C频数255例（85.0%）,A为45例（15.0%）;观察组为等位基因C 188例（78.3%）,A为52例（21.7%）。各基因型在两组中的分布经卡方检验,P〈0.05。纯合AA型（P=0.019,OR=1.963,95%CI为1.362-5.015）与杂合的CA型（P=0.023,OR=1.971,95%CI为1.117-3.752）可能增加RA的发病风险。等位基因频率在两组间存在显著性差异,A等位基因可能增加发病风险（P=0.022,OR=1.607,95%CI为1.121-3.218）。观察组基因型为CC、CA、AA者发病年龄分别为（46.3±11.6）岁、（37.5±10.3）岁、（38.8±5.9）岁,不同基因型者发病年龄有统计学差异（F=26.067,P〈0.05）,基因型为AA者发病年龄较小。观察组基因型为CC、CA、AA者男性病例数目分别为27、18、1例,不同基因型RA患者性别分布差异无统计学意义。结论 RA患者Ghrelin基因C408A位点存在多态性。基因型为AA、CA者RA发病风险高于CC者。A等位基因者发病风险增加;基因型为AA者发病年龄较小。     

血管紧张素Ⅱ1型受体基因A1166C多态性与北京地区原发性高血压的关系

该文探讨血管紧张素Ⅱ1型受体（AT1R）基因A1166C多态性与北京地区原发性高血压（EH）的关系。方法：对249例EH患者进行AT1R基因A1166C多态性测定。结果：（1）检出CC基因型1例（0．49／6），AC基因型26例（10．4％），AA基因型222例（89．29，5）；A等位基因频率为94．3；C等位基因为5．79／6。与林从容等的研究基因型分布和等位基因频率比较差异均无统计学意义；     

A T-786C polymorphism in 5'-flanking region of the endothelial nitric oxide synthase gene and endothelium-dependent arterial dilation in Type 2 diabetes.

OBJECTIVE: Several studies have shown that the T-786C polymorphism in 5'-flanking region of the endothelial nitric oxide synthase (eNOS) gene is associated with coronary artery disease in non-diabetic population. In the present study, we attempted to assess whether the T-786C polymorphism of eNOS gene is associated with endothelial dysfunction Type 2 diabetes. RESEARCH DESIGN AND METHODS: A total of 162 Type 2 diabetic men were studied. PCR/allele-specific probes were used to analyse the T-786C polymorphism of eNOS gene, and high resolution ultrasound was used to measure brachial artery diameter at rest, after reactive hyperaemia and after sublingual glyceryltrinitrate. RESULTS: The flow-mediated arterial dilation among subjects with T/C or C/C was 3.73+/-0.50%, which was significantly lower than that in subjects with T/T (4.15+/-0.49%) (P=0.000). On multiple linear regression analysis, the presence of C allele, mean blood pressure, low-density lipoprotein (LDL) and serum lipoprotein (a) [Lp(a)] were independent determinants for reduced endothelium-dependent arterial dilation (R2=0.175, P=0.0021). The flow-mediated arterial dilation in smokers with T/C or C/C was significantly lower than that in smokers with T/T (P<0.001), but not in non-smokers. In addition, the presence of C allele, LDL and Lp(a) were independent determinants for reduced endothelium-dependent arterial dilation (R2=0.258, P=0.0017) in smokers, but not in non-smokers. CONCLUSION: The C allele of T-786C polymorphism of eNOS gene is a genetic risk factor for endothelial dysfunction in Type 2 diabetic patients, especially among smokers.     

Role of the Gly460Trp polymorphism of the alpha-adducin gene in primary hypertension in Scandinavians

Previous studies have suggested that the Trp460 allele of the Gly460Trp polymorphism in the alpha-adducin gene is associated with salt sensitivity and primary hypertension. The present study was undertaken to evaluate if the Trp460 allele of this polymorphism is associated with primary hypertension in Scandinavians. To address this issue, 294 patients with primary hypertension and 265 normotensive control subjects from Sweden were examined and genotyped for the Gly460Trp polymorphism using polymerase chain reaction and restriction fragment length polymorphism methods. We then used a population of 80 patients with primary hypertension and 154 normotensive control subjects from Finland to replicate the findings. The frequency of the Trp460 allele was lower in hypertensive patients than in normotensive controls in the Swedish population (17.7% vs 23.0%; P = 0.03) and in the Finnish population (14.4% vs 19.5%; NS). Therefore we also performed a pooled analysis in which the frequency of the Trp460 allele was significantly lower in hypertensive patients than in normotensive controls (17.0% vs 21. 7%; P = 0.02). In subjects who did not receive antihypertensive medication (n = 447) there was no difference between carriers of the three different codon 460 genotypes (Trp-Trp; Trp-Gly and Gly-Gly) either for systolic (128 +/- 18; 127 +/- 15 and 129 +/- 17 mm Hg, NS) or for diastolic blood pressure (75.6 +/- 12.1; 74.7 +/- 9.3 and 75.0 +/- 10.4 mm Hg, NS). In conclusion, the lower frequency of the Trp460 allele in hypertensive patients than in normotensive controls strongly argues against a pathogenic role of this allele in primary hypertension. The results rather suggest that another variant in linkage disequilibrium with the Gly460Trp polymorphism increases susceptibility for hypertension.Journal of Human Hypertension (2000) 14, 43-46.     

A hepatic lipase gene promoter polymorphism attenuates the increase in hepatic lipase activity with increasing intra-abdominal fat in women

High hepatic lipase (HL) activity is associated with an atherogenic lipoprotein profile of small, dense LDL particles and lower HDL(2)-C. Intra-abdominal fat (IAF) is positively associated with HL activity. A hepatic lipase gene (LIPC) promoter variant (G-->A(-250)) is associated with lower HL activity, higher HDL(2)-C, and less dense LDL particles. To determine whether the LIPC promoter polymorphism acts independently of IAF to regulate HL, 57 healthy, premenopausal women were studied. The LIPC promoter A allele was associated with significantly lower HL activity (GA/AA=104+/-34 versus GG=145+/-57 nmoles x mL(-1) x min(-1), P=0.009). IAF was positively correlated with HL activity (r=0.431, P<0.001). Multivariate analysis revealed a strong relationship between both the LIPC promoter genotype (P=0. 001) and IAF (P<0.001) with HL activity. The relationship between IAF and HL activity for carriers and noncarriers of the A allele was curvilinear with the carriers having a lower apparent maximum level of plasma HL activity compared with noncarriers (138 versus 218 nmoles x mL(-1) x min(-1), P<0.001). In addition, the LIPC A allele was associated with a significantly higher HDL(2)-C (GA/AA=16+/-7 versus GG=11+/-5 mg/dL, P=0.003). We conclude that the LIPC promoter A allele attenuates the increase in HL activity due to IAF in premenopausal women.     

Apolipoprotein E gene polymorphism is related to metabolic abnormalities, but does not influence erythrocyte membrane lipid composition or sodium-lithium countertransport activity in essential hypertension

The aim of this study was to analyze the influence of the apolipoprotein E (apoE) gene polymorphism on insulin resistance and plasma lipid composition of essential hypertensive patients. A secondary objective was to analyze if differences regarding plasma lipids had an effect on the erythrocyte membrane lipid composition and the activity of the erythrocyte membrane sodium-lithium countertransport. We studied 128 untreated nondiabetic essential hypertensive patients enrolled from our outpatient clinic. We considered as hyperinsulinemic all subjects having more than 80 mU/L of plasma insulin 120 minutes after a 75-g oral glucose intake. The number of hyperinsulinemic subjects among carriers of the epsilon4 allele was higher that in epsilon4 noncarrier subjects (13 of 19 v45 of 109, P < .05; odds ratio [OR], 3.08; confidence interval [CI], 0.99-10.57). Plasma insulin at baseline and plasma insulin and glucose at 120 minutes after overload was higher in carriers of the epsilon4 allele (respectively, 17.5 +/- 6.9 v 12.4 +/- 4.9 mU/L, P < .01; 111.9 +/- 39.9 v 88.7 +/- 48.2, P < .05; and 143.8 +/- 29.3 v 121.2 +/- 30.8 mg/dL, P < .005). Subjects with the epsilon4 allele had a plasma lipid profile more atherogenic than those without this allele. This profile was mainly characterized by higher levels of low-density lipoprotein (LDL) cholesterol (150.1 +/- 31.2 v 133.0 +/- 34.3 mg/dL, P < .05) and very-low-density lipoprotein (VLDL) triglycerides (134.7 +/- 85.5 v 99.2 +/- 68.8 mg/dL, P < .05) and by lower levels of high-density lipoprotein (HDL) cholesterol (41.8 +/- 10.7 v 50.0 +/- 14.7 mg/dL, P < .05). There were no differences between groups regarding erythrocyte membrane cholesterol or phospholipids composition and sodium-lithium countertransport (SLC) activity.     

Association of the A561C E-selectin polymorphism with systemic lupus erythematosus in 2 independent populations.

OBJECTIVE: E-selectin is expressed on cytokine stimulated endothelial cells and plays an important role in leukocyte-endothelium interactions and inflammatory cell recruitment. The gene for E-selectin is located at chromosome 1q 23-25 within the linkage area for systemic lupus erythematosus (SLE). The best characterized polymorphism in E-selectin molecule is A561C, which codes for Ser128Arg. We studied the prevalence of the A561C E-selectin gene polymorphism in patients with SLE and controls from 3 different ethnic populations. METHODS: Three cohorts of patients with SLE (1987 American College of Rheumatology criteria) and matching population controls were studied. These consisted of Caucasians of British Isles descent, Caucasians of Spanish origin, and Caucasians of Turkish origin. We used polymerase chain reaction and restriction fragment length polymorphism to genotype patients and controls. RESULTS: The numbers of patients and controls in each group were: UK (113 and 148), Spanish (145 and 179), and Turkish (93 and 96), respectively. The C allele occurred more frequently in UK and Spanish patients (OR 1.76, 95% CI 1.03-3.0, p = 0.037; and OR 1.84, 95% CI 1.1-3.09, p = 0.019), but not in Turkish patients (OR 1.03, 95% CI 0.55-1.97, p = 0.91). CONCLUSION: In 2 of 3 populations studied, the E-selectin C allele was significantly more common in SLE than in controls. E-selectin may be a susceptibility gene to SLE in these populations. Its role in disease expression and longterm outcomes such as accelerated atherosclerosis requires further study.     

Influence of polymorphism (RFLP-sstI) at the apolipoprotein C-III gene locus on the lipoprotein metabolism and insulin resistance in essential hypertensive patients. Interaction between gender and genetic polymorphism

BACKGROUND AND AIM: With respect to the general population, hypertensive patients show an increase in plasma total cholesterol and triglycerides, a decrease in HDL-cholesterol (HDLc) and a higher degree of insulin resistance. Apolipoprotein C-III (apo C-III) plays a regulatory role in the catabolism of triacylglycerol-rich lipoproteins. The S2 allele has been associated with elevated plasma triglycerides concentration, blood pressure and increased risk of myocardial infarction, all of which are characteristic of an insulin resistant state. The aim of this study was to investigate the SstI polymorphism of the apo C-III gene locus on the lipoprotein metabolism, apolipoproteins and basal glucose and insulin levels in essential hypertensive patients. We also examined the influence of the S1S2 allele on blood pressure and the interaction of the mutation at the apo C-III gene and the gender. METHODS AND RESULTS: We studied 104 essential hypertensive patients (59 males and 45 females) determining the carriers of the S2 allele of the genetic polymorphism in the apo C-III gene by polymerase chain reaction, lipoprotein metabolism by standard laboratory methods and ultracentrifugation, apolipoproteins A-I and B by immunoturbidimetry and basal glucose and insulin levels by enzymatic method and radioimmunoassay, respectively. The frequency for the carriers of the SstI minor allele S2 (S1S2 genotype) was 0.17. Patients with the rare S2 allele compared with those with S1S1 allele showed higher plasma triglycerides, total cholesterol and apo B (255.9 +/- 114.6 vs 135.8 +/- 89.1; 250.6 +/- 56.6 vs 214.8 +/- 47.9 and 128.7 +/- 34.8 vs 103.1 +/- 28.6 respectively). Furthermore, basal glucose, insulin levels in S2 allele, and the rate Tg-VLDL/HDLc were increased in the same group. Subgroup analysis revealed that the association between these polymorphism and lipoprotein metabolism, apolipoprotein and basal glucose and insulin levels occurred predominantly in females. A study on the effect of the interaction between this mutation with gender revealed an additive effect on changes in total triglycerides levels. However age, blood pressure and body mass index were similar in both groups of patients (S1S1 and S1S2 genotypes). CONCLUSIONS: These results provide evidence of interaction between gender and the Sst1 polymorphism of the apo C-III on lipoprotein metabolism and insulin resistance in essential hypertensive patients. However, the studied mutation does not contribute to blood pressure levels in essential hypertensive patients (crossover study).     

脑利钠肽T-381C基因多态性与高血压的关系

目的探讨脑利钠肽T-381C基因多态性与高血压的关系。方法高血压患者(高血压组)138例,健康人(对照组)141例。两组年龄、体质量指数无差异。对两组进行血压测量,空腹采血检测血糖、总胆固醇、三酰甘油、高密度脂蛋白胆固醇和低密度脂蛋白胆固醇等。聚合酶链反应-限制性片段长度多态性(PCR-RFLP)方法进行DNA多态性分析,琼脂糖凝胶电泳判断基因型。结果检测到TY、TC、CC 3种基因型。在高血压与对照组之间基因型构成比差异有统计学意义(P<0.05)。在高血压组TC-CC基因型和C等位基因频率(30.43%和17.75%)显著高于对照组(分别为19.86%和10.64%),P=0.042和0.016。TT基因型比TC-CC基因型的空腹血糖更高,差异有统计学意义(P<0.05)。结论脑利钠肽T-381C基因多态性可能对高血压有影响,TC-CC基因型和C等位基因发生高血压的风险较大。     

Interaction between the C(-344)T polymorphism of CYP11B2 and age in the regulation of blood pressure and plasma aldosterone levels: cross-sectional and longitudinal findings of the Olivetti Prospective Heart Study

OBJECTIVE: To study the interaction between the C(-344)T polymorphism and known determinants (age, body mass and dietary sodium) of blood pressure and plasma aldosterone. DESIGN: Cross-sectional and longitudinal (1980-1995) survey of male workers in southern Italy. SETTING: Medical centre of the Olivetti factories. PARTICIPANTS: In 1995, the C(-344)T polymorphism was characterized in 811 untreated men. A subgroup of 280 participants already seen in 1980 was the object of longitudinal analysis. MAIN OUTCOME MEASURES: Blood pressure, demographic, anthropometric and biochemical variables (serum and urinary electrolytes and plasma aldosterone) and frequency of the C(-344)T polymorphism. RESULTS: In the whole population, there was no difference among genotypes for any of the variables examined. However, multiple regression showed a significant interaction between age (but not body mass or sodium intake) and genotype with regard to systolic (P = 0.03) and diastolic ( P= 0.02) pressure variability independently of covariates. Diastolic pressure increased linearly with age in carriers of the T allele (TT, P<0.001 and TC, P= 0.005), but not in CC homozygotes ( P= 0.848). In T carriers - but not in CC homozygotes - blood pressure and serum potassium increased and plasma aldosterone and serum sodium decreased across quintiles of age (P< 0.001 for all trends). In the longitudinal study, diastolic pressure increased significantly over time only in T carriers (TC+TT: +2.6 +/- 0.6, versus CC: -0.4 +/- 1.5 mmHg, P= 0.04). CONCLUSION: Inter-individual variation of blood pressure and plasma aldosterone is affected by the interaction of C(-344)T polymorphism and ageing, thus supporting a role for this variant in mechanisms affecting blood pressure regulation.     

Association analysis of the polymorphism T1128C in the signal peptide of neuropeptide Y in a Swedish hypertensive population

OBJECTIVE: The neuropeptide Y (NPY) signal peptide polymorphism T1128C has been linked to several risk factors for cardiovascular disease. The aim of the present study was to evaluate the significance of this polymorphism for cardiovascular and cerebrovascular disease outcome. DESIGN: In a prospective study cohort, 1032 hypertensive patients (174 myocardial infarction and 170 stroke patients and 688 matched controls) were analysed for the T1128C polymorphism in the NPY gene. METHODS: The dynamic allele specific hybridization (DASH) method was used for genotyping. Serum from the same participants was analysed for total cholesterol, high-density lipoprotein (HDL), low-density lipoprotein (LDL) and triglycerides. RESULTS: The frequency of the NPY T1128C polymorphism was 8.4% among patients with a myocardial infarction or stroke, as compared to 5.1% in the control group (P = 0.040). The difference remained significant after adjustment for the cardiovascular risk factors age, sex, smoking status, body mass index, systolic and diastolic blood pressure, presence of diabetes, total cholesterol, HDL, LDL and triglycerides. CONCLUSIONS: The present study indicates that the NPY T1128C polymorphism is an independent predictor for myocardial infarction and stroke in a Swedish hypertensive population.