HindIII polymorphism of lipoprotein lipase gene and risk of myocardial infarction

The purpose of this study was to determine whether HindIII restriction polymorphism found in intron 8 of lipoprotein lipase gene is associated with the onset of myocardial infarction (MI) in Russians and Tartars living in Bashkortostan. HindIII polymorphism was investigated by the polymerase chain reaction in myocardial infarction survivors (males aged under 55 years (98 Russians and 68 Tartars) and in controls (53 Russians and 80 Tartars). The distribution of genotypes and allele frequencies in the controls were as follows: the frequencies of genotypes HindIII(-/-), HindIII(+/-), and HindIII(+/+) in Russians (3.77, 49.06, and 47.17%, respectively) did not differ from those in Tartars (7.50, 51.24, and 41.25%, respectively), while the frequency of HindIII(-) allele was 28.30% in Russians and 33.13% in Tartars. Among Tartars, the HindIII(+/+) genotype was more common in myocardial infarction survivors than in controls (OR 2.03). In the Russians this genotype was not associated with the risk of MI. The frequencies of HindIII(+/+) genotype and allele HindIII(+) were significantly higher (OR 8.96 and 6.71, respectively) and frequencies of HindIII(+/-) genotype and allele HindIII(-) were lower (OR 0.13 and 0.15) in Russian patients with repeated MI. These findings indicate that HindIII polymorphism may be a genetic risk factor for MI before 55 years of age in the Tartars and for repeated MI in Russians. This association prompts genotyping of HindIII polymorphism for predicting MI recurrence in Russian survivors after MI.     

Vitamin C deficiency and risk of myocardial infarction: prospective population study of men from eastern Finland.

OBJECTIVE: To examine the association between plasma vitamin C concentrations and the risk of acute myocardial infarction. DESIGN: Prospective population study. SETTING: Eastern Finland. SUBJECTS: 1605 randomly selected men aged 42, 48, 54, or 60 who did not have either symptomatic coronary heart disease or ischaemia on exercise testing at entry to the Kuopio ischaemic heart disease risk factor study in between 1984 and 1989. MAIN OUTCOME MEASURES: Number of acute myocardial infarctions; fasting plasma vitamin C concentrations at baseline. RESULTS: 70 of the men had a fatal or non-fatal myocardial infarction between March 1984 and December 1992.91 men had vitamin C deficiency (plasma ascorbate < 11.4 mumol/l, or 2.0 mg/l), of whom 12 (13.2%) had a myocardial infarction; 1514 men were not deficient in vitamin C, of whom 58 (3.8%) had a myocardial infarction. In a Cox proportional hazards model adjusted for age, year of examination, and season of the year examined (August to October v rest of the year) men who had vitamin C deficiency had a relative risk of acute myocardial infarction of 3.5 (95% confidence interval 1.8 to 6.7, P = 0.0002) compared with those who were not deficient. In another model adjusted additionally for the strongest risk factors for myocardial infarction and for dietary intakes of tea fibre, carotene, and saturated fats men with a plasma ascorbate concentration < 11.4 mumol/l had a relative risk of 2.5 (1.3 to 5.2, P = 0.0095) compared with men with higher plasma vitamin C concentrations. CONCLUSIONS: Vitamin C deficiency, as assessed by low plasma ascorbate concentration, is a risk factor for coronary heart disease.     

Polymorphism of the apolipoprotein E gene and the risk of myocardial infarction

The apolipoprotein E (ApoE) gene polymorphism resulting from nucleotide substitutions in exon 4 was analyzed in Russian and Tatar patients with myocardial infarction (MI) from Bashkortostan. Alleles epsilon 2, epsilon 3, and epsilon 4 were identified by PCR. The genotype frequency distribution proved to be age-dependent in healthy Russians, genotype E2/3 increasing in frequency in subjects beyond 45. Russians who suffered MI under 45 had lower frequencies of genotype E3/3 (50.00% vs. 75.47% in controls of the same age, P = 0.013, OR = 0.33) and allele epsilon 3 (72.12% vs. 85.85%, P = 0.020, OR = 0.43) and a higher frequency of allele epsilon 4 (22.12% vs. 10.38%, P = 0.030, OR = 2.45). Russians who suffered MI complicated by cardiogenic shock (CS) had a significantly higher frequency of genotype E3/4 and lower frequencies of genotype E3/3 and allele epsilon 3 as compared with MI patients without CS. In Tatars, genotype E4/4 occurred at a frequency of 14.29% in patients who suffered MI under 45, and was not detected in healthy subjects of the same age (P = 0.024, OR = 17.85). Thus, the ApoE polymorphism was associated with higher risk of MI in Russians and Tatars under 45.     

Lymphotoxin-alpha gene and risk of myocardial infarction in 6,928 cases and 2,712 controls in the ISIS case-control study

Lymphotoxin-alpha (LTA) is a pro-inflammatory cytokine that plays an important role in the immune system and local inflammatory response. LTA is expressed in atherosclerotic plaques and has been implicated in the pathogenesis of atherosclerosis and coronary heart disease (CHD). Polymorphisms in the gene encoding lymphotoxin-alpha (LTA) on Chromosome 6p21 have been associated with susceptibility to CHD, but results in different studies appear to be conflicting. We examined the association of seven single nucleotide polymorphisms (SNPs) across the LTA gene, and their related haplotypes, with risk of myocardial infarction (MI) in the International Study of Infarct Survival (ISIS) case-control study involving 6,928 non-fatal MI cases and 2,712 unrelated controls. The seven SNPs (including the rs909253 and rs1041981 SNPs previously implicated in the risk of CHD) were in strong linkage disequilibrium with each other and contributed to six common haplotypes. Some of the haplotypes for LTA were associated with higher plasma concentrations of C-reactive protein (p = 0.004) and lower concentrations of albumin (p = 0.023). However, none of the SNPs or related haplotypes were significantly associated with risk of MI. The results of the ISIS study were considered in the context of six previously published studies that had assessed this association, and this meta-analysis found no significant association with CHD risk using a recessive model and only a modest association using a dominant model (with narrow confidence intervals around these risk estimates). Overall, these studies provide reliable evidence that these common polymorphisms for the LTA gene are not strongly associated with susceptibility to coronary disease.     

Interleukin 18 gene variation and risk of acute myocardial infarction

Interleukin 18 is an important mediator of inflammation and has been associated with the development and aggravation of cardiovascular diseases. We report that common variation in the interleukin 18 gene is related to acute myocardial infarction, a frequent clinical manifestation of atherosclerosis and thrombosis in coronary arteries. In a population of European, mainly (90%) German, ancestry (2136 cases with acute myocardial infarction and 1211 controls), the association was based on specific alleles and haplotypes derived from a set of six tagging single nucleotide polymorphisms. The rs1946519-G (located in the 5' upstream region), rs360717-C (exon 1), rs5744241-G (intron 1), rs1834481-C (intron 3), and rs3882891-A (intron 5) alleles (P≤0.039) and a haplotype (GCGCAG haplotype; P=0.0028) containing the GCGCA motif derived from these alleles were associated with an increased risk of AMI. Corresponding with this result, the complementary alleles (rs1946519-T, rs360717-T, rs5744241-A, rs1834481-G, and rs3882891-C) and a haplotype (TTAGCG haplotype; P=0.018) with the TTAGC motif showed protective effects. Haplotypes not including the GCGCA or TTAGC motif were not related to AMI (P≥0.22). These observations suggest that the interleukin 18 gene is a susceptibility locus for acute myocardial infarction, a finding of potential interest in the clinical practice.     

Haplotype-based case-control study of CYP4A11 gene and myocardial infarction

CYP4A11, which is a member of the cytochrome P450 family, acts mainly as an enzyme that converts arachidonic acid to 20-hydroxyeicosatetraenoic acid (20-HETE), a metabolite involved in the maintenance of cardiovascular health. Recently, it was reported that many subfamilies of CYP genes have an association with myocardial infarction (MI). The aim of the present study was to assess the association between the human CYP4A11 gene and MI, using a haplotype-based case-control study with a separate analysis of the gender groups. A total of 239 MI patients and 285 controls were genotyped for 3 single-nucleotide polymorphisms (SNPs) of the human CYP4A11 gene (rs2269231, rs1126742, rs9333025). The data obtained via haplotype-based case-control studies were assessed for 3 separate groups: total subjects, men, and women. For the total, men and women groups, the distribution of the genotypes and alleles of the 3 SNPs did not show any significant difference between the MI patients and the control subjects. For the total and the men groups, the overall distribution of the haplotypes constructed with the 3 SNPs significantly differed between the MI patients and control subjects (P < 0.001). Also, for the total and for the men, the frequency of the T-T-A haplotype constructed with the 3 SNPs was significantly lower for the MI patients than for the control subjects (both P 相似文献   

Polymorphism in chemokine receptor genes and risk of acute myocardial infarction in North Indian population

Chemokines regulates the trafficking of leukocytes to the site of inflammation hence may be implicated in cardiac events. Currently no consistent effects have been revealed their role in acute myocardial infarction (MI). The aim of current study was to investigate the impact of human chemokine receptor genetic variants, CCR5-Δ32 insertion/deletion, CCR5-59029-A/G, CX3CR1-V249I and CX3CR1-T280 M on acute MI. 230 acute MI and 300 controls were examined. Patients carrying CCR5-Δ32 genotype were at three times higher risk of developing MI odds ratio (OR, 3.24, CI 1.127–9.356, P = 0.04). Significant association was found with risk of acute MI in recipients who possessed homozygous 59029-A allele (OR 1.47, CI 1.03–2.09, P = 0.03). While CX3CR1-I249 and M280 were found to be protective in MI patients with OR 0.46, CI 0.32–0.66, P < 0.0001 and OR 0.36, CI 0.24–0.55, P < 0.0001, respectively. It might be possible that risk of acute MI is associated with genetic variation in chemokine receptors, i.e., CCR5 and CX3CR1.     

Oxidized-phospholipids in reconstituted high density lipoprotein particles affect structure and function of recombinant paraoxonase 1

Paraoxonase 1 (PON1) is an HDL-associated enzyme and exhibits anti-inflammatory, anti-diabetic, and anti-atherogenic properties. Association of PON1 to HDL particles increases the stability and activity of PON1 and is important for the normal functioning of the enzyme. HDL particles are made up of lipid and protein constituents and apolipoprotein A-I (apoA-I) is a principal protein constituent of HDL that facilitates various biological activities of HDL. In many disease conditions the oxidized phospholipid (Ox-PL) content of HDL is found to be increased and an inverse correlation between the activity of PON1 and oxidation of the HDL is observed. However, the molecular details of the inhibitory action of the Ox-PL-containing HDL on the function of PON1 are not clear yet. In this study we have assembled reconstituted HDL (rHDL) particles with and without Ox-PL and compared their effect on the structure and function of ¹³C-labeled recombinant PON1 (¹³C-rPON1) by employing attenuated total reflectance Fourier transformed infrared (ATR-FTIR) spectroscopy and enzymatic assay. Our results show that the presence of the Ox-PL in the rHDL particles alters the structure of rPON1 and decreases its lactonase activity.     

Ghrelin can bind to a species of high density lipoprotein associated with paraoxonase

Ghrelin is a 28-residue peptide hormone that is principally released from the stomach during fasting and prior to eating. Two forms are present in human plasma: the unmodified peptide and a less abundant acylated version, in which octanoic acid is attached to the third residue, a serine, via an ester linkage. The acylated form of ghrelin acts as a ligand for the growth hormone secretagogue receptor and can stimulate the release of growth hormone from the pituitary gland. It also initiates behavioral and metabolic adaptations to fasting. Here we show that an immobilized form of ghrelin specifically binds a species of high density lipoprotein associated with the plasma esterase, paraoxonase, and clusterin. Both free ghrelin and paraoxon, a substrate for paraoxonase, can inhibit this interaction. An endogenous species of ghrelin is found to co-purify with high density lipoprotein during density gradient centrifugation and subsequent gel filtration. This interaction links the orexigenic peptide hormone ghrelin to lipid transport and metabolism. Furthermore, the interaction of the esterified hormone ghrelin with a species of HDL containing an esterase suggests a possible mechanism for the conversion of ghrelin to des-acyl ghrelin.     

Plasma levels of lecithin:cholesterol acyltransferase and risk of future coronary artery disease in apparently healthy men and women: a prospective case-control analysis nested in the EPIC-Norfolk population study

LCAT plays a key role in the maturation of HDL, as evidenced by low HDL-cholesterol levels in carriers of deleterious mutations in LCAT. However, the role of LCAT in atherosclerosis is unclear. We set out to study this in a prospective study. Plasma LCAT levels, which strongly correlate with LCAT activity, were measured in baseline nonfasting samples of 933 apparently healthy men and women who developed coronary artery disease (CAD) and 1,852 matched controls who remained free of CAD during 6 year follow-up. LCAT levels did not differ between cases and controls but were higher in women than men. Stratification into LCAT quartiles revealed a positive association with plasma LDL-cholesterol and triglyceride levels in the unexpected absence of an association with HDL-cholesterol. In mixed-gender analyses, the odds ratio (OR) for future CAD in the highest LCAT quartile versus the lowest was 1.00 [confidence interval (CI): 0.76–1.29, P for linearity = 0.902], although opposite trends were observed in men and women. In fact, high LCAT levels were associated with an increased CAD risk in women (unadjusted OR 1.45, CI: 0.94–2.22, P for linearity = 0.036). In contrast to our studies in carriers of LCAT mutations, the current data show that low LCAT plasma levels are not associated with increased atherosclerosis in the general population.     

Polymorphism of angiotensinogen gene M235T in myocardial infarction and brain infarction: a meta-analysis

The angiotensinogen (AGT) gene M235T polymorphism has been reported to be associated with myocardial infarction (MI) and brain infarction (BI), but the results remain inconclusive. This meta-analysis was designed to clarify these controversies. Electronic databases were systematically searched before February 2013. A total of 38 studies with 17304 subjects met our inclusion criteria. In East Asian group, significant association was found between AGT M235T polymorphism and risk of MI (for dominant model: OR = 1.79; 95% CI = 1.04–3.06; for recessive model OR = 2.01; 95% CI = 1.21–3.36; for additive model OR = 1.79; 95% CI = 1.14–2.86) as well as BI (for dominant model: OR = 1.66; 95% CI = 1.22–2.27; for recessive model OR = 1.78, 95% CI = 1.29–2.46; for additive model: OR = 1.64, 95% CI = 1.34–2.00), while the M235T polymorphism did not impact the risk of MI in total population and other ethnicity. In the subgroup analyses by gender and age, there was lack of evidence for the association. This meta-analysis suggested an association between the M235T polymorphism and MI as well as BI in East Asian population. Further studies with larger numbers of worldwide participants are needed to understand the genetic basis of MI and BI.     

Symptoms of a first acute myocardial infarction in women and men

Background: Many studies have compared women and men for symptoms of acute myocardial infarction (AMI), but findings have been inconsistent, largely because of varying inclusion criteria, different study populations, and different methods.Objective: The purpose of this study was to analyze gender differences in symptoms in a well-defined, population-based sample of women and men who experienced a first AMI.Methods: Information on symptoms was collected from the medical charts of all patients with a first AMI, aged 25 to 74 years, who had taken part in the INTERGENE (Interplay Between Genetic Susceptibility and Environmental Factors for the Risk of Chronic Diseases) study. INTERGENE was a population-based research program on risk factors for cardiovascular disease. Medical charts were reviewed for each patient to determine the symptoms of AMI, and the prevalence of each symptom was compared according to sex.Results: The study included 225 patients with a first AMI: 52 women and 173 men. Chest pain was the most common symptom, affecting 88.5% (46/52) of the women and 94.8% (164/173) of the men, with no statistically significant difference between the sexes. Women had significantly higher rates of 4 symptoms: nausea (53.8% [28/52] vs 29.5% [51/173]; age-adjusted odds ratio [OR] = 2.78; 95% CI, 1.47–5.25), back pain (42.3% [22/52] vs 14.5% [25/173]; OR = 4.29; 95% CI, 2.14–8.62), dizziness (17.3% [9/52] vs 7.5% [13/173]; OR = 2.60; 95% CI, 1.04–6.50), and palpitations (11.5% [6/52] vs 2.9% [5/173]; OR = 3.99; 95% CI, 1.15–13.84). No significant gender differences were found in the proportions of patients experiencing arm or shoulder pain, diaphoresis, dyspnea, fatigue, neck pain, abdominal pain, vomiting, jaw pain, or syncope/lightheadedness. No significant differences were found in the duration, type, or location of chest pain. The medical charts listed numerically more symptoms in women than in men; 73.1% (38/52) of the women but only 48.0% (83/173) of the men reported >3 symptoms (age-adjusted OR = 3.26; 95% CI, 1.62–6.54).Conclusions: Chest pain is the most common presenting symptom in both women and men with AMI. Nausea, back pain, dizziness, and palpitations were significantly more common in women. Women as a group displayed a greater number of symptoms than did men.     

Distinction in the mode of receptor-mediated endocytosis between high density lipoprotein and acetylated high density lipoprotein: evidence for high density lipoprotein receptor-mediated cholesterol transfer

The interactions of high density lipoprotein (HDL) and acetylated high density lipoprotein (acetyl-HDL) with isolated rat sinusoidal liver cells have been investigated. Cellular binding of 125I-acetyl-HDL at 0 degrees C demonstrated the presence of a specific, saturable membrane-associated receptor. This receptor was affected neither by formaldehyde-treated albumin nor by low density lipoprotein modified either by acetylation or malondialdehyde, ligands known to undergo receptor-mediated endocytosis by the cells, indicating that the receptor for acetyl-HDL constitutes a distinct class among the scavenger receptors for chemically modified proteins. Parallel binding experiments using 125I-HDL also revealed the presence on these cells of a receptor for unmodified HDL. The ligand specificities of these two receptors were similar to each other except that the acetyl-HDL receptor was sensitive to polyanions such as dextran sulfate and fucoidin. Interaction of HDL with the cells at 37 degrees C was totally different from that of acetyl-HDL. Cellular binding of HDL was not accompanied by subsequent intracellular degradation of its apoprotein moiety, whereas its cholesterol moiety was significantly transferred to the cells. In contrast, acetyl-HDL was endocytosed and underwent lysosomal degradation as a holoparticle. This shift in receptor-recognition from the HDL receptor to the acetyl-HDL receptor was accomplished by acetylation of approximately 8% of the total lysine residues of HDL apoprotein. This unique difference in endocytic behavior between HDL and acetyl-HDL suggests a potential link of the HDL receptor to HDL-mediated cholesterol transfer in sinusoidal liver cells.     

The acute effect of 30 min of moderate exercise on high density lipoprotein cholesterol in untrained middle-aged men

Fifteen middle-aged, untrained (defined as no regular exercise) men (mean age 49.9 years, range 42-67) cycled on a cycle ergometer at 50 rpm for 30 min at an intensity producing 60% predicted maximum heart rate [(fc,max), where fc,max = 220 - age]. Total cholesterol (TC), high-density lipoprotein cholesterol (HDL-C), low-density lipoprotein cholesterol (LDL-C) and triglyceride (Tg) concentrations were measured from fasting fingertip capillary blood samples collected at rest, after 15 and 30 min of exercise, and at 15 min post-exercise. The mean HDL-C level increased significantly from the resting level of 0.85 mmol.l-1 to 0.97 mmol.l-1 (P < 0.05) after 15 min of exercise, increased further to 1.08 mmol.l-1 (P < 0.01) after 30 min of exercise and remained elevated at 1.07 mmol.l-1 (P < 0.01) at 15 min post-exercise. These increases represented changes above the mean resting level of 14.1%, 27.1% and 25.9% respectively. The HDL-C/LDL-C ratio increased significantly from a resting ratio of 0.20 to 0.26 after 30 min of exercise (P < 0.01) and to 0.24 at 15 min post-exercise (P < 0.05). The mean Tg level increased significantly from a resting level of 0.88 mmol.l-1 to 1.05 mmol.l-1 after 15 min, and to 1.06 mmol.l-1 after 30 min of exercise (P < 0.05 at each time). The TC/HDL-C ratio decreased significantly (P = 0.05) after 30 min of exercise and at 15 min post-exercise by 18.8% and 14%, respectively. No significant changes were observed in the levels of TC or LDL-C over time.(ABSTRACT TRUNCATED AT 250 WORDS)     

Urinary excretion of epsilondA is not predictive of cancer development: a prospective nested case-control study

Human biomonitoring of the lipid peroxidation DNA modification 1,N⁶-ethenodeoxyadenosine (εdA) excreted into urine is thought to be a potential marker for oxidative stress-related DNA damage and human cancer. We have tested this hypothesis in a prospective, nested case-control study. During the years 1984-1989, 24-h urines were collected from 1956 men in the Kuopio Ischaemic Heart Disease (KIHD) Risk Factor Study. εdA concentrations were measured by LC-MS/MS in 24-h urine samples from 47 men with cancer diagnosed at follow up until 2001 and from 31 cancer free smoking-matched control subjects. Odds ratio for having higher than control median εdA excretion rate and cancer, estimated by binary logistic regression, was 0.73 (95% CI 0.29-1.80, p=0.49). In this study, the urinary excretion of εdA provides no additional prediction of cancer development in males after controlling for smoking.