Can Suicide Attempt be Related to Problem Drinking: Cohort Study.

AIMS: Alcohol consumption is a well-established risk factor in suicidal behaviour, but there is still discussion about which factor might imply greater suicide risk-acute alcohol intoxication or being a problems drinkers. The aim of this study was to analyse the association between a suicide attempt and the drinking pattern and to evaluate the risk factors for suicide attempt among problem drinkers versus non-problem drinkers. SHORT SUMMARY: We found that problem drinking (CAGE ≥2) is an important issue in suicide attempts. Factors predicting suicide attempt among problem drinkers were male gender, younger age, being married or in a partnership status, low education and acute alcohol intoxication prior a suicide attempt. METHODS: A cohort study was performed including all cases of patients (n = 425) hospitalized in the Lithuanian University of Health Sciences after a suicide attempt. Participants completed a self-administered questionnaire that included questions on sociodemographic characteristics, the nature of the suicide attempt, the question of alcohol consumption prior to the suicide attempt and a CAGE questionnaire screening for problem drinking (CAGE ≥ 2). RESULTS: Two-thirds (70.9%) of male and 43.2% of female suicide attempters were problem drinkers. Problem drinking versus non-problem drinking increased the risk of suicide attempt especially according to gender (3.2 times for male), age (1.08 times for younger age), marital status (among married or in a partnership-1.58 times), education level (among < 12 years-2.04 times) and acute alcohol intoxication prior a suicide attempt (8.15 times-among intoxicated). CONCLUSIONS: Our results highlight that being a problem drinker as well as the use of alcohol at the time of the event is an important issue in suicide attempt,.

Association between Fibrillin1 Polymorphisms (rs2118181, rs10519177) and Transforming Growth Factor ß1 Concentration in Human Plasma.

Transforming growth factor (TGF)-ß1 is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF-ß1 levels are linked to Marfan syndrome (MFS) caused by fibrillin1 (FBN1) mutations and subsequent defects in signaling system. FBN1 single nucleotide polymorphisms (SNPs) rs2118181 and rs1059177 do not cause MFS but are associated with dilative pathology of aortic aneurysms (DPAAs). TGF-ß1 and FBN1 SNPs rs2118181 and rs1059177 are potential biomarkers for early diagnosis of DPAA. We investigated the relationship between TGF-ß1 levels in human blood plasma and FBN1 rs2118181 and rs1059177 in 269 individuals. The results showed a quantitative dependence of SNP genotype and TGF-ß1 concentration. Presence of a single rs2118181 minor allele (G) increased the amount of TGF-ß1 by roughly 1 ng/mL. Two copies of FBN1 rs1059177 minor allele (G) were required to have an additive effect on TGF-ß1 levels. We found higher TGF-ß1 concentrations in men compared with women (p = 0.001). A strong correlation between TGF-ß1 levels and FBN1 SNPs suggests that a single nucleotide substitution in FBN1 sequence might reduce bioavailability or binding properties of fibrillin-1 and have an effect on TGF-ß1 activation and cytokine concentration in blood plasma. By establishing the relationship between TGF-ß1 and FBN1 SNPs rs2118181 and rs1059177, we provide evidence that their combination might be used as molecular biomarkers to identify patients at risk for sporadic ascending aortic aneurysm and aortic dissection.

Blood Plasma TGF- ß1 Concentration in Sporadic Dilatative Pathology of Ascending Aorta: More Questions than Answers.

Transforming growth factor ß1 (TGF- ß1) is a cytokine that participates in a broad range of cellular regulatory processes and is associated with various diseases including aortic aneurysm. Increased TGF- ß1 levels are associated with Marfan syndrome (MFS) caused by FBN1 mutations and subsequent defects in signaling system. We studied TGF- ß1 levels in 62 patients with sporadic, non syndromic, dilatative pathology of ascending aorta (DPAA) and in reference group subjects (n = 212). An initial screening of 212 reference individuals identified TGF- ß1 gender discrepancies and age-dependent cytokine increase in women. Patients with DPAA had increased levels of TGF- ß1 in comparison to reference group subjects (median 7.7 ng/ml, range 2.1-25.3, and median 6.2 ng/ml, range 1.0-33.1, respectively). There is a significant association between TGF-ß1 concentration and DPAA (OR 1.084, CI 1.027-1.144, p = 0.004) but the mechanisms of cause and effect have not been established yet. Slightly increased TGF-ß1 concentrations in patients with sporadic DPAA in comparison to the reference subjects show a potential use of TGF-ß1 as a biomarker for the disease. However, cytokine dependence on age, gender, and other unknown factors among individuals with no cardiovascular complains reduces its specificity for DPAA. We would also like to raise awareness regarding the choice of methods when measuring TGF-ß1 levels with an emphasis on preanalytical phase and the choice of sample.

FBN1 polymorphisms in patients with the dilatative pathology of the ascending thoracic aorta.

OBJECTIVES: To investigate polymorphisms of the fibrillin-1 (FBN1) gene (namely, rs2118181, rs1036477, rs10519177, rs755251 and rs4774517) in a case-control study for dilatative pathology of the ascending thoracic aorta (DPATA) from Lithuanians. METHODS: We studied 312 patients who had undergone aortic reconstructive surgery for DPATA. These patients were sub-divided according to the phenotypes of their DPATA into (i) ascending aortic aneurysm (n = 160), (ii) post-stenotic dilatation of the ascending aorta due to aortic valve stenosis (n = 79) and (iii) Stanford A dissection (n = 73). The reference group (n = 472) was recruited from a random sample screened within epidemiological studies of the Lithuanian population. FBN1 polymorphisms were studied by real-time polymerase-chain-reaction amplification. RESULTS: Patients within the aortic dissection sub-group had significantly higher minor allele frequencies in all five FBN1 single nucleotide polymorphism (SNPs) studied versus reference group subjects (P < 0.0001). Minor allele frequencies in SNPs rs2118181, rs1036477 were significantly higher in those with aortic aneurysm when compared with the reference group (P = 0.007). Thus, minor alleles of FBN1 SNPs studied were significantly associated with aortic dissection with odds ratios (ORs) 2.59-2.13, P < 0.001, while SNPs rs2118181 and rs1036477 with an increased risk of ascending aortic aneurysm [OR 1.67, confidence interval (CI) 95% 1.61-2.40]. The association of FBN1 genotypes with each phenotype of DPATA was assessed using logistic regression models adjusted for gender, age and hypertension. The additive model best fitted SNPs rs2118181 and rs1036477 in association with the ascending aortic aneurysm sub-group (OR 1.70, CI 95% 1.17-2.46) or the Stanford A dissection sub-group (OR 2.64, CI 95% 1.66-4.19). A recessive model fitted best the association between SNPs rs10519177, rs755251, rs4774517 and Stanford A dissection (OR 4.31, CI 95% 2.06-9.01). There were no significant associations between all studied FBN1 SNPs and post-stenotic or bicuspid aortic dilatation. CONCLUSIONS: Our study provides evidence for the following: (i) FBN1 SNPs rs2118181, rs1036477, rs10519177, rs4774517, rs755251 may increase susceptibility to aortic dissections and (ii) FBN1 SNPs rs2118181, rs1036477 to the formation of aortic aneurysms. Thus, these SNPs might be considered as biomarkers for identifying patients at risk for ascending aortic aneurysm and aortic dissection.

The Role of Matrix Metalloproteinases Polymorphisms in Age-Related Macular Degeneration.

BACKGROUND: Matrix metalloproteinases (MMP) are responsible for the degradation of extracellular matrix components and play an important role in the physiological and pathological remodeling of tissues. PURPOSE: To assess the impact of MMP-2 Rs2285053 (C->T), MMP-3 Rs3025039 (5A->6A), and MMP-9 Rs3918242 (C->T) single nucleotide polymorphism on the development of early age-related macular degeneration (AMD). METHODS: The study group comprised 148 patients with AMD, and the control group enrolled 526 randomly selected persons. The genotyping of MMP-3 Rs3025039, MMP-2 Rs2285053, and MMP-9 Rs3918242 was performed by using the real-time PCR method. RESULTS: The frequency of the MMP-2 (-735) C/T and MMP-3 (-1171) 5A/6A genotypes did not differ significantly between the patients with AMD and the control group, while the MMP-9 (-1562) C/C genotype was more frequently detected in patients with AMD than the control group (73.7% vs. 64.6%, p=0.048). Logistic regression analysis showed that the MMP-9 (-1562) C/C genotype increased the likelihood of developing early AMD (OR=1.51, 95% CI: 1.01-2.21; p=0.046). After the subdivision into the groups by age, a significant difference only in the frequency of the MMP-9 (-1562) C/C genotype was found comparing the AMD patients and the control group younger than 65 years (79.7% vs. 66.4%, p=0.039). CONCLUSIONS: Only MMP-9 Rs3918242 (C->T) single nucleotide polymorphism was found to play a significant role in the development of AMD, and the effect was more pronounced at the age of less than 65 years.

Left ventricular remodelling after acute myocardial infarction: impact of clinical, echocardiographic parameters and polymorphism of angiotensinogen gene.

INTRODUCTION: The development of left ventricular remodelling after acute myocardial infarction is a predictor of heart failure and mortality. The purpose of the present study was to assess whether the polymorphism of angiotensinogen (AGT) gene with threonine (T) instead of methionine (M) at amino acid 235 in exon 2 (M235T) had effects on cardiac remodelling after acute myocardial infarction. METHODS: One hundred and forty-one patients (mean age 56.4±11.1 years) with a first acute myocardial infarction were enrolled. Within 24-72 hours of the onset of the symptoms and at a four month period two-dimensional echocardiography was performed. Remodelling was defined as a 20% increase from the baseline in left ventricular end-diastolic volume. The genotypes of the study group were compared with the reference group (n=1010) genotypes. AGT M235T polymorphism was determined using polymerase chain reaction amplification. RESULTS: At follow-up, 49 patients (34.7%) were classified as having left ventricular remodelling. Anterior localization of the infarct (p=0.008), leucocyte count at admission (p=0.040), global left ventricular longitudinal strain (p=0.021) and MM genotype of AGT (p=0.024) were independent predictors of ventricular remodelling after myocardial infarction. CONCLUSIONS: Anterior wall infarction, increased leucocyte count, decreased longitudinal strain of left ventricular and polymorphism of AGT M235T may predict remodelling after myocardial infarction.

Matrix metalloproteinase-3 gene polymorphism and dilatative pathology of ascending thoracic aorta.

Matrix metalloproteinase-3 (MMP-3) degrades extracellular matrix and may lead to development of dilatative pathology of ascending thoracic aorta. Expression of MMP-3 depends upon the 5A/6A polymorphism in the promoter region. An increased number of 5A alleles leads to high expression of MMP-3. Thus, objective of the study was to determine whether the 5A/6A polymorphism in the promoter region of MMP-3 gene is associated with the development of dilatative pathology of ascending thoracic aorta. We studied 76 patients (age ranged from 31 to 81 years; median age, 64 years) who underwent aortic reconstruction surgery due to dilatative pathology of ascending thoracic aorta and a random sample of the population (n=604) aged 25-64 years, all from Lithuania. DNA was analyzed by using real-time polymerase chain reaction to genotype polymorphism 5A/6A at a position -1171 of the MMP3 gene promoter. The prevalence of MMP-3 genotypes was similar in the group of dilatative pathology of ascending thoracic aorta and random sample of population. The frequency of 5A allele did not differ significantly between both groups and was 0.506 and 0.514, respectively. Male carriers of 5A/5A genotype were significantly younger compared with those with the 6A/6A genotype. In conclusion, the frequency of MMP-3 promoter 5A/6A genotypes did not differ between the group of patients with dilatative pathology of ascending thoracic aorta and the random sample of population, but the males with dilatative pathology of ascending thoracic aorta and 5A/5A genotype required aortic reconstruction surgery at the younger age than the males carrying 6A/6A genotype in the MMP-3 promoter region.