Association of a polymorphism of the ecNOS gene with myocardial infarction in a subgroup of Turkish MI patients

In this study we examined a possible association between a 27 base pair (bp)-repeat polymorphism in intron 4 of the ecNOS gene and myocardial infarction (MI) in a subgroup of the Turkish population. We compared MI and control groups for the frequencies of the ecNOS alleles and their genotypes. The frequency of the ecNOS 4a/a and 4a/b genotypes was found to be significantly higher in the MI group than in the control group. Interestingly, the frequency of the ecNOS 4a/b polymorphism was found to be significantly higher in the selected MI group (patients with no known secondary risk factors) than in the control and non-selected MI group. We found that the patients with MI had the frequency of the a/a genotype 4.3%, of the a/b genotype 26.6% and the b/b genotype 69.1%. The controls, however, showed only 0.6% for a/a, 18.0% for a/b and 81.4% for the b/b genotype (P < 0.001; chi2 = 13.626). In this study, we show that myocardial infarction is associated with one subtype of ecNOS gene polymorphism.     

CYP4A11基因多态性与心肌梗死相关

目的 研究在不同性别中CYP4A11基因多态性与心肌梗死的关系.方法 166例心肌梗死患者和158例对照组,选择CYPA11基因的3个SNPs(rs9332978、rs3890011和rs1126742),应用TaqMan SNP基因分型法进行基因分型,并应用病例对照的研究方法进行相关性分析.结果 rs3890011的基因分型在心肌梗死组和对照组之间的分布存在明显差异(P＜0.05),心肌梗死组携带GG基因型(GG vs CC+ GC)高于对照组(P＜0.05),在排除吸烟、高血压、糖尿病等混杂因素后,仍存在显著性差异(95％ CI:1.138～2.432,P＜0.01).结论 CYP4A11基因的rs3890011多态性与心肌梗死相关,rs3890011的GG基因型可作为心肌梗死易感基因标记.     

Addressing the link between paraoxonase-1 gene variants and the incidence of early onset myocardial infarction

Introduction

The enzyme paraoxonase-1 (PON1) represents an endogenous defense mechanism against vascular oxidative stress, thereby contributing to the prevention of atherosclerosis. Several polymorphisms have been reported in the PON1 gene, including Q192R. PON1 phenotype is commonly expressed as the paraoxonase/arylesterase ratio (PON/ARE). The major aim of this study was to investigate the association between PON1 Q192R polymorphism, PON1 phenotypes and the incidence of early-onset acute myocardial infarction (AMI) in Egyptians.

Material and methods

The study subjects consisted of 102 AMI patients and 72 age-matched healthy controls. Genotyping and enzyme activities were determined using PCR-RFLP and kinetic spectrophotometric assays, respectively.

Results

The genotype distribution for the PON1 gene was significantly different between AMI patients (QQ = 38.24%, QR = 49.02%, RR = 12.75%) and controls (QQ = 66.67%, QR = 25%, RR = 8.33%). Allele frequencies were also significantly different between patients (Q = 62.75%, R = 37.25%) and controls (Q = 79.17%, R = 20.83%). The genotypes QR and RR showed higher risk for AMI compared to the homozygous QQ (odds ratio (OR) = 3.231, p < 0.001). The average PON/ARE ratio in MI patients (1.187 ±0.1) did not differ significantly from controls (1.118 ±0.26). However, it showed a significant difference among different genotypes in both AMI patients (QQ = 0.91 ±0.11, QR = 1.09 ±0.11 and RR = 2.65 ±0.4) (p = 0.0002) and controls (QQ = 0.68 ±0.1, QR = 1.07 ±0.11 and RR = 4.89 ±2.84) (p < 0.0001).

Conclusions

PON1 192R allele represents an independent risk factor for early-onset AMI in Egyptians, and PON1 Q192R polymorphism modulates the paraoxonase phenotype.     

Low coronary driving pressure early in the course of myocardial infarction is associated with subendocardial remodelling and left ventricular dysfunction

Subendocardial remodelling of the left ventricular (LV) non-infarcted myocardium has been poorly investigated. Previously, we have demonstrated that low coronary driving pressure (CDP) early postinfarction was associated with the subsequent development of remote subendocardial fibrosis. The present study aimed at examining the role of CDP in LV remodelling and function following infarction. Haemodynamics were performed in Wistar rats immediately after myocardial infarction (MI group) or sham surgery (SH group) and at days 1, 3, 7 and 28. Heart tissue sections were stained with HE, Sirius red and immunostained for alpha-actin. Two distinct LV regions remote to infarction were examined: subendocardium (SE) and interstitium (INT). Myocyte necrosis, leucocyte infiltration, myofibroblasts and collagen volume fraction were determined. Compared with SH, MI showed lower CDP and LV systolic and diastolic dysfunction. Necrosis was evident in SE at day 1. Inflammation and fibroplasia predominated in SE as far as day 7. Fibrosis was restricted to SE from day 3 on. Inflammation occurred in INT at days 1 and 3, but at a lower grade than in SE. CDP correlated inversely with SE necrosis (r = -0.65, P = 0.003, at day 1), inflammation (r = -0.76, P < 0.001, at day 1), fibroplasia (r = -0.47, P = 0.04, at day 7) and fibrosis (r = -0.83, P < 0.001, at day 28). Low CDP produced progressive LV expansion. Necrosis at day 1, inflammation at days 3 and 7, and fibroplasia at day 7 correlated inversely with LV function. CDP is a key factor to SE integrity and affects LV remodelling and function following infarction.     

Genetic variant R952Q in LRP8 is associated with increased plasma triglyceride levels in patients with early-onset CAD and MI

We previously identified a novel locus for plasma triglyceride (TG) levels on chromosome 1p31-32 by genome-wide linkage analysis in the GeneQuest population with familial and premature coronary artery disease (CAD). Here we tested a hypothesis that variants in LRP8, a gene that is under the 1p31-32 linkage peak and associated with risk of familial and premature CAD and increased platelet activation, are associated with TG levels. Seven tagSNPs that cover the entire LRP8 gene were characterized in 358 GeneQuest Caucasian probands. Only SNP R952Q (rs5174) was associated with TG levels (P-adj = 0.0016), and this finding was replicated in one other independent population of 134 patients with early-onset myocardial infarction (males <45; females <55; P-adj = 0.0098). TG levels were higher in the group with higher body mass index (BMI ≥ 25) than in the group with lower BMI (BMI < 25). The association was significant in the overweight group (P-adj = 0.0029) or in the smoking group (P-adj = 0.0004), but not in the group with normal BMI or without smoking history. These results suggest that genetic variant R952Q of LRP8 is associated with increased plasma TG levels in patients who are overweight and have premature CAD/MI and history of smoking.     

血栓素合酶基因Pro1770Leu多态性与新疆维吾尔族心肌梗死的相关性研究

目的 探讨血栓素合酶基因CYP5A1 Pro1770Leu多态性与新疆维吾尔族心肌梗死的相关性.方法 采用聚合酶链反应-限制性片段长度多态性方法,对315例心肌梗死患者和218名健康受试者血栓素合酶基因第13外显子Pro1770Leu位点进行分析,同时进行血清血栓素B2(thromboxane B2,TXB2)水平测定.结果 血栓素合酶基因第13外显子Pro1770Leu在病例组和健康对照组中基因型频率分别为:CC型0.933和0.977,TC型0.067和0.023,病例组TC型高于对照组(P＜0.05),且T等位基因频率显著高于对照组(P＜0.05),血清TXB2水平病例组较对照组明显增高,差异具有统计学意义(P＜0.05);TC基因型携带者血清TXB2水平较CC基因型者增高,差异具有统计学意义(P＜0.05).结论 血栓素合酶基因第13外显子Pro1770Leu基因多态性和新疆维吾尔族心肌梗死的发生具有相关性,可能与基因变异导致的血清TXB2水平增高有关.     

The apolipoprotein B signal peptide insertion/deletion polymorphism is not associated with myocardial infarction in Norway

The three-amino acid insertion/deletion (I/D) polymorphism in the apoB signal peptide (27 amino acid versus 24 amino acid signal peptide) was evaluated as a possible risk factor for myocardial infarction (MI) in a case-control study population comprising 238 MI survivors and 547 controls. In controls, homozygotes for the deletion allele (DD) had the highest mean levels of both total cholesterol and low density lipoprotein (LDL) cholesterol (LDLC), the homozygotes for the insertion allele (II) had the lowest mean values, while the heterozygotes (ID) had intermediate mean levels (p < 0.05). In MI survivors, the trend was similar, but only differences in mean LDLC levels were statistically significant (p < 0.05). No differences in genotype frequencies were detected between cases and controls in univariate analysis or in multivariate logistic regression analysis. Despite the results from the lipid analyses, we conclude that the I/D polymorphism in the apoB signal peptide is unlikely to be of major importance for MI risk in relatively young Norwegians.     

DNA repair gene XRCC1 Arg399Gln polymorphism is associated with increased risk of uterine leiomyoma

BACKGROUND: DNA repair gene XRCC1 Arg399Gln polymorphism has been associated with the risk of several human tumours. In the present study we investigated whether the XRCC1 polymorphism is related to the risk of uterine leiomyoma, the most common neoplasm of the female genital tract. METHODS: Three hundred and twenty-seven patients with uterine leiomyoma and 197 normal controls were enrolled, and XRCC1 genotyping was determined by PCR and restriction fragment length polymorphism. RESULTS: The proportions of individuals homozygous for 399Arg allele, heterozygous and homozygous for the 399Gln allele were 85.8%, 13.7% and 0.5% among the control group, and 46.2%, 53.2% and 0.6% in those with leiomyoma (P < 0.001), respectively. Logistic regression analysis (after adjusting for age, parity, menarche age and body mass index) showed a significant increased risk of uterine leiomyoma in women with the Arg/Gln genotype versus the Arg/Arg genotype (odds ratio 6.79; 95% confidence interval 4.20-10.99; P < 0.001). CONCLUSIONS: In Korean women, the 399Gln polymorphism of XRCC1 is associated with an increased risk of uterine leiomyoma.     

Single nucleotide polymorphisms in VEGF gene are associated with an increased risk of osteosarcoma

We aimed to assess whether the five common SNPs can affect the risk of osteosarcoma, and its association with demographic characteristics of osteosarcoma. 165 osteosarcoma patients and 330 cancer-free controls were enrolled into our study. Five common SNPs in VEGF gene, -2578C/A (rs699947), -1156G/A (rs1570360), +1612G/A (rs10434), +936C/T (rs3025039) and -634G/C (rs2010963), were detected by polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP). Conditional logistic regression analyses found that individuals with AA genotype and A allele of rs699947 were associated with an increased risk of osteosarcoma. Individuals with GG genotype and G allele of rs2010963 were associated with an increased risk of osteosarcoma. By stratified analysis, AA genotype of rs699947 was associated with an increased risk of osteosarcoma in those with shorter age, males and a family history of cancer, and GG genotype of rs2010963 was correlated with an increased risk of osteosarcoma in those with shorter age, females and a family history of cancer. Our study suggests that rs699947 and rs2010963 polymorphisms may play a role in the pathogenesis of osteosarcoma.     

基质金属蛋白酶9基因-1562C/T多态性与新疆维吾尔族心肌梗死的相关性研究

目的 探讨新疆维吾尔族人群基质金属蛋白酶9(matrix metalloproteinase 9,MMP9)基因启动子区-1562C/T多态性与心肌梗死(myocardialinfarction,MI)发病的相关性.方法 选择经皮冠状动脉造影检查确诊的维吾尔族心肌梗死患者347例(MI组),以同期冠脉造影阴性、排除冠心病诊断的403例维吾尔族患者为对照组.采用聚合酶链反应-限制性片段长度多态性方法对所有纳入对象MMP9基因-1562C/T多态性进行分析,比较两组间MMP9基因多态性频率分布的差异,并结合造影情况,探讨MMP9基因多态性与MI发病及冠脉狭窄程度的关系.结果 MI组CT+TT基因型频率(27.67%)明显高于对照组(14.14%),两组差异具有统计学意义(χ2=20.99,P＜0.01),T等位基因频率在MI组和对照组分别为15.71%、7.56%(χ2=24.57,P＜0.01).Logistic回归分析显示,携带-1562T等位基因的个体发生MI的风险大约升高2倍(OR=2.009,95%CI:1.250～3.230);携带T等位基因合并糖尿病的个体发生MI的风险明显升高(OR=3.714,95%CI:1.299～10.773).MMP9基因-1562C/T多态性分布与MI冠脉狭窄程度差异无统计学意义.结论 MMP9基因-1562C/T多态性可能与新疆维吾尔族人群MI茇病具有相关性;-1562T等位基因可能是MI遗传易感性的基因标记之一;-1562T等位基因与糖尿病在MI发生中具有协同作用.MMP9基因-1562C/T多态性与MI冠脉狭窄程度无关.

Abstract：

Objective To investigate the association between matrix metalloproteinase 9 gene (MMP9)- 1562C/T polymorphism and myocardial infarction (MI) in Uighur population of Xinjiang.Methods A total of 347 patients with MI evidenced by coronary arteriography, and 403 controls free from coronary artery disease with normal angiograms were recruited for the study. Polymerase chain reactionrestriction fragment length polymorphism (PCR-RFLP) was used to detect the -1562C/T functional promoter polymorphism of the MMP9 gene. The relationship between the polymorphism and the severity of coronary arterial stenosis was analyzed. Results The results showed that the frequency of CT and TT genotypes in patients with MI (27. 67%) was significantly higher than that in controls (14. 14%). The frequencies of the - 1562T allele were 15. 71% and 7. 56% in the MI group and the control group respectively (2 = 24.57, P＜0.01). Logistic regression analysis indicated that the T allele carriers (CT+TT) had significantly increased risk of MI compared with the CC carriers (OR=2. 009, 95%CI: 1. 250-3. 230). Individuals carrying the -1562T allele with diabetes mellitus were at an increased risk of MI (OR=3. 714, 95% CI: 1. 299-10. 773). The frequencies of CT and TT genotypes were not significantly different among MI patients with one, two and three or more significantly diseased vessels (χ2 =0. 491, P=0. 782). Conclusion The - 1562C/T polymorphism in the MMP9 gene promoter is associated with the susceptibility to MI in the Uighur population of Xinjiang. The T allele might be a risk factor of MI. And there was a coordinated effect between the -1562T allele and diabetes mellitus in the development of MI.The -1562C/T polymorphism may not be a predictor of the severity of coronary atherosclerosis.     

Atopic dermatitis is not independently associated with nonfatal myocardial infarction or stroke among US women

We aimed to determine the association between atopic dermatitis (AD) and cardiovascular events in the Nurses' Health Study 2, a cohort of US women. We used logistic regression models to calculate age‐ and multivariate‐adjusted odds ratios (OR) and 95% confidence intervals (CI) for the associations between history of AD and nonfatal MI and nonfatal stroke. Of the 78 702 participants in our analysis, 7916 (10%) had a history of AD. There were 392 and 391 cases of nonfatal MI and stroke, respectively. AD was not associated with MI in age‐ or multivariate‐adjusted analyses. AD was significantly associated with stroke in the age‐adjusted analysis (OR 1.38, 95% CI 1.03–1.85). This was no longer significant in multivariate models that adjusted for hypertension, hypercholesterolemia and diabetes (OR 1.31, 95% CI 0.98–1.76) and atopic comorbidities (OR 1.17, 95% CI 0.86–1.58). AD was not independently associated with nonfatal MI or stroke in this study.     

凝血因子Ⅴ和Ⅶ基因多态性与冠心病的初步研究

目的　观察凝血因子 (coagulation factor ,F )、 (coagulation factor ,F )基因多态性在中国汉族人群中的分布及其与冠心病 (coronary heartdisease,CHD)的关系。方法　应用聚合酶链反应和限制性内切酶片段长度多态性技术检测了 2 34例 CHD患者和 2 10名正常对照者的 F 、F 基因型 ,结合选择性冠状动脉造影结果探讨两者的关系。结果　 F 等位基因 R、Q和 H7、H6频率在冠心病组和对照组分别为 94 .6 %、5 .6 %、70 .3%、2 9.7%和 91.9%、8.1%、6 0 .9%、39.1%。基因型频率符合 Hardy-Weinberg平衡定律。R35 3Q和 HVR4基因型频率和等位基因频率在 CHD组和对照组 ,狭窄血管支数之间比较差异均无显著性。 R35 3Q基因型频率和等位基因频率在非心肌梗塞组和心肌梗塞组比较差异有显著性 (χ2 =4 .711,P<0 .0 5 ,OR=0 .37,95 % CI:0 .15～ 0 .94 ) ,而 HVR4基因多态在两组间比较差异无显著性(χ2 =0 .14 2 ,P>0 .0 5 )。冠心病组和对照组均没有发现 F L eiden突变。结论　F R35 3Q基因多态中的 Q等位基因可能是对抗心肌梗塞的保护因子     

IGF-I gene variability is associated with an increased risk for AD

Insulin-like growth factor I (IGF-I), a neuroprotective factor with a wide spectrum of actions in the adult brain, is involved in the pathogenesis of Alzheimer's disease (AD). Circulating levels of IGF-I change in AD patients and are implicated in the clearance of brain amyloid beta (Aβ) complexes. To investigate this hypothesis, we screened the IGF-I gene for various well known single nucleotide polymorphisms (SNPs) covering % of the gene variability in a population of 2352 individuals. Genetic analysis indicated different distribution of genotypes of 1 single nucleotide polymorphism, and 1 extended haplotype in the AD population compared with healthy control subjects. In particular, the frequency of rs972936 GG genotype was significantly greater in AD patients than in control subjects (63% vs. 55%). The rs972936 GG genotype was associated with an increased risk for disease, independently of apolipoprotein E genotype, and with enhanced circulating levels of IGF-I. These findings suggest that polymorphisms within the IGF-I gene could infer greater risk for AD through their effect on IGF-I levels, and confirm the physiological role IGF-I in the pathogenesis of AD.     

血清IL-6、IL-8在急性心肌梗死缺血-再灌注过程中的动态变化及其临床意义

目的 :探讨血清IL 6、IL 8在急性心肌梗死 (AMI)早期及溶栓治疗过程中的动态变化及其意义。方法 :采用放射免疫分析法对 30例AMI患者入院当时、溶栓前及溶栓后不同时间点的血清IL 6、IL 8进行检测 ,分析其与心肌缺血 再灌注间的关系。结果 :与健康对照组相比 ,所有AMI患者的IL 6、IL 8水平于入院时即已开始升高 ,溶栓治疗后继续升高 ,其中IL 6高峰期在溶栓后 12～ 2 4小时 ,IL 8在 4～ 8小时 ;溶栓再通组升高更明显 (P <0 0 5 ) ;伴有心源性休克 ,急性心力衰竭及严重心律失常并发症的AMI患者较无并发症者增高明显 (P <0 0 5 )。结论 :观察细胞因子IL 6、IL 8动态变化规律有助于判定AMI病情及估价溶栓治疗效果。     

The angiotensin-converting enzyme (ACE) genetic polymorphism: its relationship with plasma ACE level and myocardial infarction

The angiotensin-converting enzyme (ACE) is a key factor in the production of angiotensin II and in the degradation of bradykinin, two important peptides involved in vascular physiology. Plasma and cellular ACE levels in humans are influenced by an insertion (I)/deletion (D) polymorphism of the ACE gene, the ACE I/D polymorphism. The D allele has a frequency of approximately 0.53 in Caucasian populations and is codominantly associated with higher levels of ACE. We have studied this polymorphism in a large multicenter case-control study (the ECTIM study) and found that the D allele was associated with a parental history of fatal myocardial infarction (MI) in the controls and was more frequent in male patients with MI than in controls. This case-control difference was compatible with a codominant effect of allele D on the risk of MI with relative risks of 1.57 for DD vs II and 1.26 for ID vs II (test for trend p < 0.003). In subjects at low risk of MI (plasma ApoB < 1.25 g/1 and body mass index < 26 kg/m²), the relative risk of DD vs ID + II was 2.7 (p < 0.0005). The results were very homogeneous in the four populations included in the study. In a family study, using linkage-segregation analysis, we have shown that the ACE I/D polymorphism is a marker for an unknown functional polymorphism (ACE S/s) which appears to be a new independent risk factor for MI.     

前列环素合酶基因多态性与新疆维吾尔族心肌梗死的相关性

目的 探讨前列环素合酶基因C1117A多态性与新疆维吾尔族心肌梗死的相关性.方法 采用聚合酶链反应.限制性片段长度多态性方法,对310例心肌梗死患者和306名健康受试者前列环素合酶基因第8外显子C1117A位点进行分析,同时进行血清6-酮前列腺素F1α水平测定.结果 前列环素合酶基因第8外显子C1117A在病例组和健康对照组中基因型频率分别为:CC型0.70和0.62,CA型0.26和0.32,AA型0.03和0.06,两组CC基因型频率差异具有统计学意义(P＜0.05),且病例组C等位基因频率高于对照组(P＜0.01),而CA和AA基因型差异无统计学意义(P＞0.05).血清6-酮前列腺素F1α水平病例组较对照组明显降低,差异具有统计学意义(P＜0.05);CC基因型携带者血清6-酮前列腺素F1α水平较CA和AA基因型者降低,差异具有统计学意义(P＜0.05).结论 前列环素合酶基因第8外显子C1117A基因多态性和新疆维吾尔族心肌梗死的发生具有相关性,可能和基因变异导致的血清前列环素水平降低有关.     

Lack of association of genetic variants in the LRP8 gene with familial and sporadic myocardial infarction

Coronary artery disease (CAD) and myocardial infarction (MI) have a genetic basis, but the precise genetic underpinning remains controversial. Recently, an association of the LRP8 R952Q polymorphism (rs5174) with familial premature CAD/MI was reported. We analysed rs5174 (or the perfect proxy rs5177) in 1,210 patients with familial MI and 1,015 controls from the German MI Family study, in 1,926 familial CAD (1,377 with MI) patients and 2,938 controls from the Wellcome Trust Case Control Consortium (WTCCC) MI/CAD cohort, in 346 CAD patients and 351 controls from the AtheroGene study and in 295 men with incident CAD and 301 controls from the Prospective Epidemiological Study of MI study and found no evidence for association in any of the populations studied. In the WTCCC and the German MI Family studies, additional single-nucleotide polymorphisms in the LRP8 gene were analysed and displayed no evidence for association either. Electronic supplementary material  The online version of this article (doi:) contains supplementary material, which is available to authorized users. Wolfgang Lieb, Tanja Zeller, Massimo Mangino, Jeanette Erdmann, and Laurence Tiret contributed equally.