Usefulness of combining complement factor H and C-reactive protein genetic profiles for predicting myocardial infarction (from the Rotterdam Study)

Complement factor H (CFH) is an important regulator of the complement cascade. Binding of C-reactive protein (CRP) to CFH augments the ability of CFH to downregulate the effect of complement in atherosclerotic lesions. The CFH Tyr402His polymorphism has been suggested to influence the ability of CFH to bind CRP. We hypothesized that the combined presence of unfavorable CRP and CFH genetic profiles is associated with risk of myocardial infarction (MI). The Rotterdam Study is a population-based cohort study in 7,983 men and women aged > or =55 years. The CFH Tyr402His (rs1061170) polymorphism was determined (His(402) allele 37%), and using 3 tagging polymorphisms (rs1130864, rs1205, and rs3093068), CRP haplotypes were inferred (1 = CTC, 2 = TCC, 3 = CCC, 4 = CCG; frequencies of 33%, 32%, 30%, and 6%, respectively). Participants were grouped by CFH genotype (TyrTyr [reference], TyrHis, and HisHis) and CRP haplotype (haplotype 1 homozygotes [reference], haplotype 2 carriers, haplotype 3 carriers, and haplotype 4 carriers), which resulted in a total of 12 groups. CFH His(402) homozygotes who were also CRP haplotype 3 carriers had an age- and gender-adjusted hazard ratio of 5.9 (95% confidence interval 2.1 to 16.5) to develop MI compared with the reference group. In conclusion, this population-based study suggests that the combined presence of unfavorable CFH and CRP genetic profiles is associated with risk of MI.     

A common polymorphism in the complement factor H gene is associated with increased risk of myocardial infarction: the Rotterdam Study.

OBJECTIVES: This study was designed to investigate the association between a common polymorphism (Tyr402His, rs1061170) in the complement factor H (CFH) gene and risk of coronary heart disease. BACKGROUND: The evidence that inflammation is an important mechanism in atherogenesis is growing. C-reactive protein (CRP), complement factors, and complement regulatory factors have all been linked to coronary heart disease. The CFH gene is an important regulator of the alternative complement cascade. We investigated its association with coronary heart disease. METHODS: The study was embedded in the Rotterdam Study, a prospective population-based study among men and women aged 55 years and over. A total of 5,520 participants without history of coronary heart disease was genotyped for the Tyr402His polymorphism of the CFH gene. Cox proportional hazards analysis was used to determine risk of myocardial infarction for Tyr402His genotypes. RESULTS: Mean age among participants was 69.5 years (SD 9.1 years). The overall frequency of the His allele was 36%; genotype frequencies were 41%, 45%, and 14% for TyrTyr, TyrHis, and HisHis, respectively. During a mean follow-up period of 8.4 years, 226 myocardial infarctions occurred. After adjustment for age, gender, established cardiovascular risk factors, and CRP level, HisHis homozygotes had a hazard ratio of 1.77 (95% confidence interval 1.23 to 2.55) for myocardial infarction. Total cholesterol level, diabetes mellitus, and smoking modified the effect. The Tyr402His polymorphism was not associated with established cardiovascular risk factors or CRP level. CONCLUSIONS: Our data suggest that the CFH gene determines susceptibility to myocardial infarction. This finding underscores the importance of the alternative complement system in cardiovascular disease.     

Inflammation and stress-related candidate genes,plasma interleukin-6 levels,and longevity in older adults

Interleukin-6 (IL-6) is an inflammatory cytokine that influences the development of inflammatory and aging-related disorders and ultimately longevity. In order to study the influence of variants in genes that regulate inflammatory response on IL-6 levels and longevity, we screened a panel of 477 tag SNPs across 87 candidate genes in >5000 older participants from the population-based Cardiovascular Health Study (CHS). Baseline plasma IL-6 concentration was first confirmed as a strong predictor of all-cause mortality. Functional alleles of the IL6R and PARP1 genes were significantly associated with 15%–20% higher baseline IL-6 concentration per copy among CHS European–American (EA) participants (all p < 10⁻⁴). In a case/control analysis nested within this EA cohort, the minor allele of PARP1 rs1805415 was nominally associated with decreased longevity (p = 0.001), but there was no evidence of association between IL6R genotype and longevity. The PARP1 rs1805415 – longevity association was subsequently replicated in one of two independent case/control studies. In a pooled analysis of all three studies, the “risk” of longevity associated with the minor allele of PARP1 rs1805415 was 0.79 (95%CI 0.62–1.02; p = 0.07). These findings warrant further study of the potential role of PARP1 genotype in inflammatory and aging-related phenotypes.     

Host polymorphisms in interleukin 4, complement factor H, and C-reactive protein associated with nasal carriage of Staphylococcus aureus and occurrence of boils

BACKGROUND: Staphylococcus aureus is capable of persistently colonizing the vestibulum nasi. We hypothesized that polymorphisms in host inflammatory response genes and genetic variation in S. aureus contribute to susceptibility to S. aureus carriage and infection. METHODS: The prevalence of persistent nasal carriage of S. aureus in 3851 participants aged 61-101 years was 18% (678 of 3851 participants), whereas 73% of volunteers (2804 of 3851) were not colonized. A total of 1270 individuals had boils. Polymorphisms in TNFA (C -863T), IL4 (C -542T), CFH (Tyr402His), and CRP (C1184T, C2042T, and C2911G) were determined. Genetic similarity among 428 S. aureus isolates was determined by use of amplified fragment length polymorphism analysis (AFLP)-mediated genotyping. RESULTS: The IL4 -524 C/C host genotype was associated with an increased risk of persistent S. aureus carriage, irrespective of S. aureus AFLP genotype. The CRP haplotype 1184C; 2042C; 2911C was overrepresented in individuals who were not colonized . In individuals with boils, carriers of the CFH Tyr402 variant, and the CRP 2911 C/C genotype were overrepresented. CONCLUSION: Persistent carriage of S. aureus is influenced by genetic variation in host inflammatory response genes. As would be expected in multifactorial host-microbe interactions, these effects are limited. Interestingly, host genotype was associated with the carriage of certain S. aureus genotypes. Apparently, a close interaction between host and bacterial determinants are prerequisites for long-term colonization.     

Distinct pharmacodynamics of insulin glargine and insulin detemir: Crossover comparison in Type 1 and Type 2 diabetic patients on basal-bolus regimen

Two hundred and eighty six subjects with cardiovascular diseases and 147 healthy newborns were studied. P53 codon 72 polymorphism was determined by DNA analysis.The association between BMI and diabetes depends on p53 polymorphism: Odds Ratio shows a high significant association between BMI and diabetes in *Arg/*Arg subjects (p = 0.00001). No significant association is observed in *Pro allele carriers (p = 0.203).     

Early intravenous beta-blockers in patients with acute coronary syndrome—A meta-analysis of randomized trials

Background

Intravenous (IV) beta-blockade is currently a Class IIa recommendation in early management of patients with acute coronary syndromes (ACS) without obvious contraindications.

Methods

We searched the PubMed, EMBASE and the Cochrane Register for Controlled Clinical Trials for randomized clinical trials from 1965 through December, 2011, comparing intravenous beta-blockers administered within 12 hours of presentation of ACS with standard medical therapy and/or placebo. The primary outcome assessed was the risk of short-term (in-hospital mortality-with maximum follow up duration of 90 days) all-cause mortality in the intervention group versus the comparator group. The secondary outcomes assessed were ventricular tachyarrhythmias, myocardial reinfarction, cardiogenic shock, and stroke. Pooled treatment effects were estimated using relative risk with Mantel–Haenszel risk ratio, using a random-effects model.

Results

Sixteen studies enrolling 73,396 participants met the inclusion ⁄ exclusion criteria. In- hospital mortality was reduced 8% with intravenous beta-blockers, RR = 0.92 (95% CI, 0.86–1.00; p = 0.04) when compared with controls. Moreover, intravenous beta-blockade reduced the risk of ventricular tachyarrhythmias (RR = 0.61; 95 % CI 0.47–0.79; p = 0.0003) and myocardial reinfarction (RR = 0.73, 95 % CI 0.59–0.91; p = 0.004) without increase in the risk of cardiogenic shock, (RR = 1.02; 95% CI 0.77–1.35; p = 0.91) or stroke (RR = 0.58; 95 % CI 0.17–1.98; p = 0.38).

Conclusions

Intravenous beta-blockers early in the course of appropriate patients with ACS appears to be associated with significant reduction in the risk of short-term cardiovascular outcomes, including a reduction in the risk of all-cause mortality.     

Modulating effects of matrix metalloproteinase-3 and -9 polymorphisms on aortic stiffness and aortic root dilation in patients after tetralogy of Fallot repair

Matrix metalloproteinases (MMPs) are capable of degrading extracellular matrix proteins, which are important determinants of arterial stiffness. This study aimed to test the hypothesis that MMP-3 and MMP-9 polymorphisms may modulate aortic stiffness and magnitude of aortic root dilation in patients after surgical repair of tetralogy of Fallot (TOF). We analyzed the MMP-3 promoter and MMP-9 −1562 C > T polymorphism in 79 TOF patients aged 19.9 ± 9.5 years and determined their associations with aortic stiffness and sinotubular dimension. Genotypic and allelic frequencies of MMP-3 for the 6A6A genotype and MMP-9 for the T allele did not differ between patients and published control data (all p > 0.05). For the MMP-3 locus, patients with a 6A6A genotype and those with a 6A6A/5A6A genotype had similar aortic stiffness (p = 0.60), heart-femoral pulse wave velocity (p = 0.63), and z score of sinotubular junction (p = 0.81). For the MMP-9 locus, the −1562T allele carriers had significantly lower aortic stiffness (p = 0.005), slower heart-femoral pulse wave velocity (p = 0.03), and smaller z score of sinotubular junction (p = 0.047). Multivariate linear regression identified MMP-9 polymorphism (β = −0.31, p = 0.005) as a significant correlate of aortic stiffness after adjustments for age at study, age at operation, sex, body mass index, systolic and diastolic blood pressures, and MMP-3 polymorphism. In conclusion, MMP-9 but not MMP-3 polymorphism exerts a modulating influence on aortic stiffness and aortic root dilation in patients after TOF repair.     

The glucocorticoid receptor gene polymorphism N363S predisposes to more severe toxic side effects during pediatric acute lymphoblastic leukemia (ALL) therapy

The survival rates in childhood acute lymphoid leukemia (ALL) have improved dramatically; however, patients still suffer from a variety of drug-related toxicities. Individualized therapy regimens promise the least toxic therapy regimen with the best hematologic outcome. Our aim was to investigate whether increased individual glucocorticoid sensitivity due to the N363S polymorphism of the glucocorticoid receptor increased susceptibility to steroid-related toxicities during ALL therapy. A total of 346 pediatric ALL patients were involved in the present study. N363S carrier status was investigated by allele-specific PCR. Clinical and laboratory signs of glucocorticoid-related toxicities, Day 8 prednisone response, and 5-year event-free survival were analyzed and compared retrospectively. Thirty-two of the 346 patients were heterozygous carriers (9.2 %). Hepatotoxicity (31.3 vs. 11.2 %, p = 0.004, carriers and non-carriers, respectively) and glucose metabolism abnormalities (18.8 vs. 3.8 %, p = 0.001, carriers and non-carriers, respectively) were significantly more frequent among carriers. There was no difference in the incidence of hypertension and encephalopathy/psychosis among carriers and non-carriers. Carriers were also more prone to have a combination of toxicities. All 363S carriers were good prednisone responders (100 %) and had significantly better 5-year event-free survival rates (93.1 vs. 71.86 %, p = 0.012), whereas among non-carriers there were more poor prednisone responders (8.28 %) and worse 5-year event-free survival rates. Patients with the N363S polymorphism in the glucocorticoid receptor are more prone to steroid-related toxicity during ALL therapy and should be monitored more closely. Patients with N363S polymorphism of the glucocorticoid receptor may be appropriate candidates for inclusion in the design of individualized therapies.     

Risk factors and incidence of stroke and MACE in Chinese atrial fibrillation patients presenting to emergency departments: A national wide database analysis

Background

Contemporary clinical risk stratification schemata for predicting stroke and thromboembolism in patients with atrial fibrillation (AF) are largely derived from western cohorts. The purpose of the present study is to assess the potential risk factors for stroke and major adverse cardiac events (MACE) in a large population of Chinese AF patients presenting to emergency department.

Methods

The Chinese AF registry is a multicenter, prospective, observational study with 1 year follow up. Patients who presented to an emergency department with atrial fibrillation or atrial flutter were recruited from November 2008 to October 2011. The MACE included all cause mortality, stroke, non-central nervous system systemic embolism and major bleed.

Results

A total of 2016 AF patients (1104 women) were included in the final analysis. Multivariate Cox regression analysis showed that the risk factors for stroke were female gender (1.419 (1.003–2.008), p = 0.048), age ≥ 75 (2.576 (1.111–4.268), p < 0.001), previous stroke/TIA (2.039 (1.415–2.939), p < 0.001), LVSD (1.700 (1.015–2.848), p = 0.044) and previous major bleeding (2.481 (1.141–5.397), p = 0.022). For MACE, age ≥ 75 (3.042 (2.274–4.071), p < 0.001), heart failure (1.371 (1.088–1.728), p = 0.008), previous stroke/TIA (1.560 (1.244–1.957), p < 0.001), LVSD (1.424 (1.089–1.862), p = 0.010) and COPD (1.393 (1.080–1.798), p = 0.011) were independent risk factors. History of hypertension and diabetes was not associated with the events, neither stroke nor MACE. For non-anticoagulation patients, the c-statistic for predicting stroke was 0.685 (0.637–0.732) and for MACE was 0.717 (0.687–0.746), respectively.

Conclusions

We demonstrated that, except for the traditional risk factors, clinicians should pay more attention to patients with prior major bleeding or COPD in Chinese AF patients presenting to emergency department.     

Female gender and contrast-induced nephropathy in primary percutaneous intervention for ST-segment elevation myocardial infarction

Background

Patients undergoing primary percutaneous coronary intervention (PCI) are at high risk for contrast-induced nephropathy (CIN), a complication that has been demonstrated to negatively affect outcomes. It has been suggested that, when compared to males, female patients present higher incidence of CIN and higher mortality after primary PCI. However, the specific role of gender in this setting remains ill-defined given its complex interplay with several co-morbidities and clinical characteristics. We investigated the relationship of patients' variables, including gender, with CIN and mortality after primary PCI.

Methods

In a single center study in 323 consecutive patients undergoing primary PCI, the development of CIN and mortality during an 18-month median follow-up period was assessed. CIN was defined as an increase in serum creatinine (≥ 25% or ≥ 0.5 mg/dl) from baseline occurring at any time during the first 3 post-procedural days.

Results

CIN occurred in 23 female and 26 male patients (25.0% vs 11.2%, p = 0.003), while cumulative mortality was 10.6%. Women presented unfavorable basal characteristics and underwent myocardial reperfusion less quickly. At multivariable analysis, reduced left ventricular ejection fraction (LVEF) (odds ratio [OR] 7.32 95% confidence interval [CI]: 2.60–21, p < 0.001) and female gender (OR 2.49 95%CI 1.22–5.07, p = 0.01) predicted CIN, whereas the occurrence of CIN (hazard ratio [HR] 3.65 95%CI 1.55–8.59, p = 0.003) and a Mehran risk score (MRS) ≥ 6 (HR 1.76 95%CI 1.13–2.74, p = 0.01) independently predicted long-term mortality.

Conclusions

After primary PCI, female gender and LVEF are associated with an increased risk of CIN, whereas MRS and development of CIN predict long-term mortality.     

Sense of coherence (SOC) related to health and mortality among the very old: The Umeå 85+ study

We describe associations between sense of coherence (SOC) and sense of well-being, diseases, physical function and the predictive value of SOC on depression and mortality. The study included 190 participants, aged 85-103 years. Linear correlation analysis was used for relationships between SOC scores and continuous variables. The effects of SOC score on 1- and 4-year mortality, as well as on depression at the 5-year follow-up, were investigated using Cox regression models. The mean SOC score was 71.8 ± 10.2 (±S.D.). SOC score was positively related to well-being (p ≤ 0.001). Heart failure (p = 0.009), chronic obstructive pulmonary disease (p = 0.015), depression (p = 0.015), and osteoarthritis (p = 0.032) were significantly associated with low SOC scores, as were high scores on the Geriatric Depression Scale (GDS) (p = 0.002). One-year mortality was significantly associated with the SOC score (OR = 0.945, confidence interval (CI) = 0.898-0.995, p = 0.032), while the 4-year mortality was not (OR = 0.995, CI = 0.973-1.018, p = 0.674). The SOC score did not predict depression at 5-year follow-up (OR = 0.977, CI = 0.937-1.018, p = 0.267). Strong SOC was associated with well-being in this group of old people. Low SOC was found among those with diseases known to have a negative influence on daily life.     

Association of systolic blood pressure levels with cardiovascular events and all-cause mortality among older adults taking antihypertensive medication

Introduction

The aim of the study was to identify the association of systolic blood pressure (SBP) levels with cardiovascular events, all-cause mortality, and falls among elderly persons taking antihypertensive medication.

Methods

US adults ≥ 45 years of age taking antihypertensive medication enrolled in the REGARDS study were categorized into 3 age groups: 55–64, 65–74 and ≥ 75 years old and baseline on-treatment SBP levels. Our primary analyses focused on incident cardiovascular disease (CVD) (n = 9787) and all-cause mortality (n = 13,948).

Results

During follow-up, 530 (5.4%) participants had CVD events and 2095 (15%) participants died. After multivariable adjustment among participants ≥ 75, the incidence of CVD per 1000 person-years (95% confidence interval) was 16.9 (11.1–25.7), 13.4 (9.2–19.7), 11.6 (7.6–17.7), 17.8 (11.2–27.5) and 36.7 (26.6–50.8) at SBP levels of < 120, 120–129, 130–139, 140–149, and ≥ 150 mm Hg, respectively. For the same SBP categories, the adjusted CVD incidence rates were 9.3 (7.2–12.0), 10.0 (8.1–12.3), 9.4 (7.5–11.8), 14.0 (11.0–17.8), and 16.4 (12.5–21.4), respectively, among participants 55–64 years, and 16.5 (13.6–21.5), 17.4 (14.8–20.6), 19.2 (16.4–22.5), 22.3 (18.6–26.9), and 27.6 (22.7–33.4), respectively, for participants 65–74 years. Among participants aged 55–64 and 65–74 years, a linear association was present between higher SBP categories and all-cause mortality risk (each p-trend < 0.001). In contrast, for participants ≥ 75 years no association was present between SBP and all-cause mortality (p-trend = 0.319). No association was observed between SBP and falls among participants in all age groups.

Conclusions

Among adults aged ≥ 55 taking antihypertensive medication, SBP between 120 and 139 mm Hg was significantly associated with a reduced risk for cardiovascular and all-cause mortality outcomes.     

The obesity paradox in men with coronary heart disease and heart failure: The role of muscle mass and leptin

Aims

We have investigated the role of muscle mass, natriuretic peptides and adipokines in explaining the obesity paradox.

Background

The obesity paradox relates to the association between obesity and increased survival in patients with coronary heart disease (CHD) or heart failure (HF).

Methods

Prospective study of 4046 men aged 60–79 years followed up for a mean period of 11 years, during which 1340 deaths occurred. The men were divided according to the presence of doctor diagnosed CHD and HF: (i) no CHD or HF ii), with CHD (no HF) and (iii) with HF.

Results

Overweight (BMI 25–9.9 kg/m²) and obesity (BMI ≥ 30 kg/m²) were associated with lower mortality risk compared to men with normal weight (BMI 18.5–24.9 kg/m²) in those with CHD [hazards ratio (HR) 0.71 (0.56,0.91) and 0.77 (0.57,1.04); p = 0.04 for trend] and in those with HF [HR 0.57 (0.28,1.16) and 0.41 (0.16,1.09; p = 0.04 for trend). Adjustment for muscle mass and NT-proBNP attenuated the inverse association in those with CHD (no HF) [HR 0.78 (0.61,1.01) and 0.96 (0.68,1.36) p = 0.60 for trend) but made minor differences to those with HF [p = 0.05]. Leptin related positively to mortality in men without HF but inversely to mortality in those with HF; adjustment for leptin abolished the BMI mortality association in men with HF [HR 0.82 (0.31,2.20) and 0.99 (0.27,3.71); p = 0.98 for trend].

Conclusion

The lower mortality risk associated with excess weight in men with CHD without HF may be due to higher muscle mass. In men with HF, leptin (possibly reflecting cachexia) explain the inverse association.     

Association of angiotensin II type 1 receptor gene A1166C polymorphism with the presence of diabetes mellitus and metabolic syndrome in patients with documented coronary artery disease

Background

There are relatively limited data available on the genetic susceptibility to diabetes mellitus and metabolic syndrome in the Iranian population. We have therefore investigated the association between the angiotensin II type I receptor gene polymorphism (AT₁R/A1166C) and the presence of diabetes mellitus and metabolic syndrome in a well defined group of patients.

Methods

Patients with angiographically defined coronary artery disease (CAD) (n = 309) were evaluated for the presence of AT₁R/A1166C polymorphism. These patients were classified into subgroups with (n = 164, M/F: 109/55) and without (n = 145, M/F: 84/61) diabetes mellitus. The AT₁R polymorphism was assessed using a polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) based method.

Results

There was a higher frequency of polymorphic genotypes (AC + CC) in the diabetic compared with the non-diabetic group (p = 0.01). When determined for each gender separately, this difference remained significant in the males (p = 0.04) but not in females (p = 0.09). With regard to the allele frequencies, the C allele was significantly higher and the A allele frequency was lower in the diabetic group (p = 0.01). This remained significant after gender segregation for males (p = 0.01) but not females. In the binary logistic regression analysis, only serum fasting glucose was found as the independent predictor for the presence of diabetes in the CAD patients (β = 1.16, p < 0.001 for total population and β = 1.29, p < 0.001 for male subjects). There was no significant difference in genotype or allele frequencies between subgroups with and without metabolic syndrome, this being unaffected by gender or the definition of metabolic syndrome used apart from a significantly lower frequency of C allele in male subjects with metabolic syndrome defined by the NCEP ATP III criteria (p = 0.04).

Conclusion

The AT₁R/A1166C polymorphism may be associated with the presence of diabetes mellitus in male subjects with documented CAD.     

Revisiting a classical clinical sign: Jugular venous ultrasound

Background

Increased jugular venous pressure, reflecting the increased right atrial pressure, is a classical sign of heart failure (HF) but clinical assessment may be difficult.

Methods

In ambulatory patients with HF and control subjects, jugular vein diameter (JVD) was measured using a linear high-frequency ultrasound probe (10 MHz) at rest, during a Valsalva manoeuvre and during deep inspiration. JVD ratio was calculated as diameter during Valsalva to that at rest.

Results

211 patients (mean age 70 years; mean left ventricular ejection fraction 43%) and 20 controls were included. JVD (median and inter-quartile [IQR] range) at rest was 0.17 (0.15–0.20) cm in controls and 0.23 (0.17–0.33) cm in patients with HF (p = 0.012), JVD ratio was 6.3 (4.3–6.8) in controls and 4.4 (2.7–5.8) in patients with HF (p = 0.001).With increasing quartiles of plasma NT-proBNP, JVD at rest rose (0.20 (0.15–0.23) cm, 0.21 (0.16–0.29) cm, 0.25 (0.18–0.35) cm and 0.34 (0.20–0.53) cm (P = < 0.001), whilst JVD ratio decreased (5.4 (4.2–6.4), 4.4 (3.5–6.3), 3.9 (2.4–5.4) and 2.8 (1.7–4.7); p = < 0.001). JVD ratio correlated with log (NT-proBNP) (r = − 0.39, p = < 0.001), LV filling pressures (E/E′, r = − 0.33, p = < 0.001) and left atrial volume (r = − 0.21, p = 0.002). In a multivariable regression model, only trans-tricuspid gradient and TAPSE were independently associated with JVD ratio (R² = 0.27).

Conclusions

Distension of the JV at rest relative to the maximum diameter during a Valsalva manoeuvre (JVD ratio) identifies patients with heart failure who have higher plasma NT-proBNP levels, right ventricular dysfunction and raised pulmonary artery pressure     

Opisthorchis felineus liver fluke invasion is an environmental factor modifying genetic risk of atopic bronchial asthma

According to epidemiological observations, Opisthorchis felineus liver fluke invasion is negatively associated with the development and severity of allergic diseases in endemic regions of Russia. We hypothesized that the invasion is an important factor in gene–environmental interactions (GEI) underlying allergy. To prove this, we tested 10 single nucleotide polymorphisms of immune response modifying genes in 428 individuals stratified by atopic bronchial asthma presence and O. felineus invasion. Using regression models, a statistically significant interaction between the rs6737848 polymorphism of SOCS5 gene and O. felineus invasion was observed (p_int = 0.001, OR = 5.66, 95% CI 1.96–16.31 for dominant model; p_int = 0.003; OR = 4.38, 95% CI 1.68–11.45 for additive model). The interaction is based on the statistically significant association between the SOCS5 gene and atopic bronchial asthma in patients without O. felineus infection, while no such association is seen in patients infected by the helminth. These data confirm for the first time the importance of the helminth invasion as an environmental factor influencing the association between genetic factors and atopic bronchial asthma. In particular, O. felineus diminishes the risk of atopic bronchial asthma associated with the SOCS5 gene polymorphism.     

LCT-13910C > T polymorphism-associated lactose malabsorption and risk for colorectal cancer in Italy

Background

The activity of epithelial lactase (LCT) associates with a polymorphism 13910 bp upstream the LCT-encoding gene (LCT-13910C > T). The relationship between LCT-13910C > T polymorphism and risk for colorectal cancer is unclear.

Aims

We examined the relationship between the LCT-13910C > T polymorphism causing lactose intolerance and risk for colorectal cancer/polyps onset in the Italian population.

Patients and methods

793 subjects (306 with colorectal cancer, 176 with polyps and 311 controls) were genotyped for the LCT-13910C > T variant by TaqMan real time-PCR.

Results

Lactose malabsorption linked to the CC genotype did not associate with an increased risk for either colorectal cancer (OR = 1.041; 95% CI = 0.751–1.442; p = 0.868) or polyps (OR = 0.927; 95% CI = 0.630–1.363; p = 0.769). There was no association with colorectal cancer/polyps site. 60% of the subjects overall bore the CC genotype.

Conclusion

In the Italian population the LCT-13910C > T polymorphism is not associated to the risk for colorectal cancer or polyps.     

Prognostic role of stress/rest myocardial perfusion scintigraphy in patients with cardiac syndrome x

Aim

The prognostic utility of myocardial perfusion scintigraphy (MPS) in patients with angiographically normal coronary arteries has not been evaluated yet. Our aim was to determine the prognostic role of positive MPS in patients with angina, positive exercise test and smooth coronary arteries (syndrome X).

Methods

A total of 156 patients with angina, positive exercise test, positive MPS and normal coronary arteries and 172 patients with angina and positive exercise test who had negative MPS were selected for study. The primary endpoint was combined all-cause mortality and hospitalizations for cardiac causes. The secondary endpoint was hospitalization for cardiac causes.

Results

Kaplan–Meier analysis showed a greater (p = 0.001) incidence of the primary endpoint in patients with positive MPS, compared to those with negative MPS. Additionally, Kaplan–Meier analysis for cardiovascular hospitalization showed a significant difference (p = 0.003) between the two groups. Cox regression analysis, adjusted for age, sex, BMI and antianginal therapy confirmed a significant risk increase for patients with positive MPS, with a hazard ratio (HR) = 3.20 (CI 95%: 1.14–9.02; p = 0.028). Cox analysis for cardiovascular hospitalization also showed a significant risk increase for patients with positive MPS (HR = 3.19; CI 95%: 1.13–9.00; p = 0.03). Finally, Cox analysis showed that patients with positive MPS tend to have a higher risk to remain symptomatic in the follow-up period (HR = 1.614; CI 95%: 0.999–2.607; p = 0.51).

Conclusions

This study shows that inducible myocardial hypoperfusion at MPS in patients with syndrome X could discriminate patients with a more severe prognosis, especially in terms of further hospitalization and symptomatic burden.     

-94 ins/del ATTG NFKB1 gene variant is associated with lower susceptibility to myocardial infarction

Background and aims

An imbalance of Nuclear Factor Kappa B (NFкB) and Inhibitor Kappa B (IкB) is involved in various human diseases including atherogenesis. We aimed to evaluate the relationship between NFKB1 and NFKBIA polymorphism and susceptibility to myocardial infarction (MI).

Methods and results

Genotyping was performed for NFKB1 and NFKBIA gene variants in 253 subjects (86 patients affected by myocardial infarction and 167 control subjects). In 40 patients, biopsy specimens were taken from the left ventricle area of presumed ischemia for p50, p65 and IкBα quantification. The allele frequency and genotype distribution of NFKBIA gene polymorphism did not differ between MI and control group while control subjects had a higher D allele frequency of -94 ins/del ATTG NFKB1 polymorphism, compared to the MI group (P < 0.001; OR = 0.304; 95% CI = 0.177-0.522). Subjects carrying the D allele had significantly lower plasma fibrinogen and CRP (C-reactive protein) levels compared to no carriers (P < 0.05). Fibrinogen-genotype interaction was found to have a significant effect on susceptibility to myocardial infarction. Myocardial p50 (r = 0.627; P = 0.012) and p65 (r = 0.683; P = 0.005) levels significantly correlated with plasma fibrinogen levels while subjects carrying the D allele of the NFкB1 gene variant had lower myocardial p50 (P = 0.007) and p65 (P = 0.009) levels compared to no carriers.

Conclusion

-94 ins/del ATTG NFKB1 gene variant may contribute to lower MI susceptibility via the potential reduction of activated NFкB which in turn is related to plasma inflammatory marker reduction.     

Seroprevalence,disease awareness,and risk factors for Toxocara canis infection among primary schoolchildren in Makoko,an urban slum community in Nigeria

In this study, we investigated the seroprevalence of Toxocara canis infection in southern Nigeria, which previously was unknown, in addition to evaluating disease awareness and potential risk factors for schoolchildren in an urban slum community. In total, 366 primary schoolchildren were investigated for the presence of anti-Toxocara IgG antibodies. Blood was collected and screened by a Western blot analysis based on the excretory–secretory antigens of larval T. canis (TcES), targeting low molecular weight bands of 24–35 kDa specific for T. canis. Children were considered seropositive if their serum reacted with TcES when diluted to a titer of 1:32. Questionnaires concerning possible risk factors were given to the schoolchildren to acquire data on this infection. The overall seroprevalence of Toxocara infection was 86.1% (315/366). The logistic regression analysis of risk factors showed that children's age (odds ratio (OR) = 2.88, 95% confidence interval (CI) = 1.08–7.66, p = 0.03), contact with dogs (OR = 0.51, 95% CI = 0.28–0.94, p = 0.03), the age of the dog (OR = 0.34, 95% CI = 0.18–0.68, p = 0.002), the feeding location of the dog (OR = 0.31, 95% CI = 0.12–0.79, p = 0.01), the consumption of raw vegetables (OR = 0.89, 95% CI = 0.54–1.48, p = 0.004), and the drinking of unboiled water (OR = 0.48, 95% CI = 0.26–0.90, p = 0.02) were risk factors associated with Toxocara infection. Although there was a high awareness of dogs being hosts of some parasites in this study, not much was known about T. canis. This is the first serological investigation of T. canis infection among primary schoolchildren in southern Nigeria. The high seroprevalence recorded is an indication of high transmission with the consequent risk of visceral or ocular larval migrans and neurologic toxocariasis in these children. Our findings suggest the need for prompt interventional measures, particularly health education on personal hygiene.