Association of VEGF-1499C -> T polymorphism with diabetic nephropathy in type 1 diabetes mellitus

Vascular endothelial growth factor (VEGF) is reported to be implicated in the development of diabetic nephropathy. We performed a case-control study to determine if VEGF-2578C -> A, VEGF-1499C -> T, and VEGF-635G -> C single-nucleotide polymorphisms (SNPs) in the VEGF gene are associated with predisposition to diabetic nephropathy in type I diabetes. Genomic DNA was obtained from Irish type I diabetic individuals with nephropathy (cases, n=242) and those without nephropathy (controls, n=301), in addition to 400 healthy control samples. These samples were genotyped for the three SNPs using TaqMan or Pyrosequencing technology. Chi-squared analyses revealed no significant differences in genotype or allele frequencies in cases versus controls for VEGF-2578C -> A (genotype, P=.58; allele, P=.52) and VEGF-635G -> C (genotype, P=.58; allele, P=.33). However, a positive association with diabetic nephropathy was observed for the VEGF-1499T allele in the Northern Ireland population (P

Association of LETM1 and MRPL36 Contributes to the Regulation of Mitochondrial ATP Production and Necrotic Cell Death

Leucine zipper/EF hand-containing transmembrane-1 (LETM1) is a mitochondrial inner membrane protein that was first identified in Wolf-Hirschhorn syndrome, and was deleted in nearly all patients with the syndrome. LETM1 encodes for the human homologue of yeast Mdm38p, which is a mitochondria-shaping protein of unclear function. Here, we describe LETM1-mediated regulation of mitochondrial ATP production and biogenesis. We show that LETM1 overexpression can induce necrotic cell death in HeLa cells, in which LETM1 reduces mitochondria) biogenesis and ATP production. LETM1 acts as an anchor protein and associates with mitochondrial ribosome protein L36. Adenovirus-mediated overexpression of LETM1 reduced mitochondrial mass and expression of many mitochondrial proteins. LETM1-mediated inhibition of mitochondrial biogenesis enhanced glycolytic ATP supply and activated protein kinase B activity and cell survival signaling. The expression levels of LETM1 were significantly increased in multiple human cancer tissues compared with normals. These data suggest that LETM1 serves as an anchor protein for complex formation with the mitochondrial ribosome and regulates mitochondrial biogenesis. The increased expression of LETM1 in human cancer suggests that deregulation of LETM1 is a key feature of tumorigenesis. [Cancer Res 2009;69(8):3397-404]

Genome-wide association of early-onset myocardial infarction with single nucleotide polymorphisms and copy number variants

We conducted a genome-wide association study testing single nucleotide polymorphisms (SNPs) and copy number variants (CNVs) for association with early-onset myocardial infarction in 2,967 cases and 3,075 controls. We carried out replication in an independent sample with an effective sample size of up to 19,492. SNPs at nine loci reached genome-wide significance: three are newly identified (21q22 near MRPS6-SLC5A3-KCNE2, 6p24 in PHACTR1 and 2q33 in WDR12) and six replicated prior observations1-4 (9p21, 1p13 near CELSR2-PSRC1-SORT1, 10q11 near CXCL12, 1q41 in MIA3, 19p13 near LDLR and 1p32 near PCSK9). We tested 554 common copy number polymorphisms (>1% allele frequency) and none met the pre-specified threshold for replication (P < 10-3). We identified 8,065 rare CNVs but did not detect a greater CNV burden in cases compared to controls, in genes compared to the genome as a whole, or at any individual locus. SNPs at nine loci were reproducibly associated with myocardial infarction, but tests of common and rare CNVs failed to identify additional associations with myocardial infarction risk.

Evidence of association of APOE with age-related macular degeneration: a pooled analysis of 15 studies.

Age-related macular degeneration (AMD) is the most common cause of incurable visual impairment in high-income countries. Previous studies report inconsistent associations between AMD and apolipoprotein E (APOE), a lipid transport protein involved in low-density cholesterol modulation. Potential interaction between APOE and sex, and smoking status has been reported. We present a pooled analysis (n = 21,160) demonstrating associations between late AMD and APOe4 (odds ratio [OR] = 0.72 per haplotype; confidence interval [CI]: 0.65-0.74; P = 4.41×10(-11) ) and APOe2 (OR = 1.83 for homozygote carriers; CI: 1.04-3.23; P = 0.04), following adjustment for age group and sex within each study and smoking status. No evidence of interaction between APOE and sex or smoking was found. Ever smokers had significant increased risk relative to never smokers for both neovascular (OR = 1.54; CI: 1.38-1.72; P = 2.8×10(-15) ) and atrophic (OR = 1.38; CI: 1.18-1.61; P = 3.37×10(-5) ) AMD but not early AMD (OR = 0.94; CI: 0.86-1.03; P = 0.16), implicating smoking as a major contributing factor to disease progression from early signs to the visually disabling late forms. Extended haplotype analysis incorporating rs405509 did not identify additional risks beyond e2 and e4 haplotypes. Our expanded analysis substantially improves our understanding of the association between the APOE locus and AMD. It further provides evidence supporting the role of cholesterol modulation, and low-density cholesterol specifically, in AMD disease etiology.

The Geography of Conflict and Death in Belfast, Northern Ireland

The conflict known as the oTroubleso in Northern Ireland began during the late 1960s and is defined by political and ethno-sectarian violence between state, pro-state, and anti-state forces. Reasons for the conflict are contested and complicated by social, religious, political, and cultural disputes, with much of the debate concerning the victims of violence hardened by competing propaganda-conditioning perspectives. This article introduces a database holding information on the location of individual fatalities connected with the contemporary Irish conflict. For each victim, it includes a demographic profile, home address, manner of death, and the organization responsible. Employing geographic information system (GIS) techniques, the database is used to measure, map, and analyze the spatial distribution of conflict-related deaths between 1966 and 2007 across Belfast, the capital city of Northern Ireland, with respect to levels of segregation, social and economic deprivation, and interfacing. The GIS analysis includes a kernel density estimator designed to generate smooth intensity surfaces of the conflict-related deaths by both incident and home locations. Neighborhoods with high-intensity surfaces of deaths were those with the highest levels of segregation ( 90 percent Catholic or Protestant) and deprivation, and they were located near physical barriers, the so-called peacelines, between predominantly Catholic and predominantly Protestant communities. Finally, despite the onset of peace and the formation of a power-sharing and devolved administration (the Northern Ireland Assembly), disagreements remain over the responsibility and ocommemorationo of victims, sentiments that still uphold division and atavistic attitudes between spatially divided Catholic and Protestant populations.

Association of polymorphisms in the hepatocyte growth factor gene promoter with keratoconus

Purpose. Keratoconus is a progressive disorder of the cornea that can lead to severe visual impairment or blindness. Although several genomic regions have been linked to rare familial forms of keratoconus, no genes have yet been definitively identified for common forms of the disease. Methods. Two genome-wide association scans were undertaken in parallel. The first used pooled DNA from an Australian cohort, followed by typing of top-ranked single-nucleotide polymorphisms (SNPs) in individual DNA samples. The second was conducted in individually genotyped patients, and controls from the USA. Tag SNPs around the hepatocyte growth factor (HGF) gene were typed in three additional replication cohorts. Serum levels of HGF protein in normal individuals were assessed with ELISA and correlated with genotype. Results. The only SNP observed to be associated in both the pooled discovery and primary replication cohort was rs1014091, located upstream of the HGF gene. The nearby SNP rs3735520 was found to be associated in the individually typed discovery cohort (P = 6.1 × 10 ). Genotyping of tag SNPs around HGF revealed association at rs3735520 and rs17501108/rs1014091 in four of the five cohorts. Meta-analysis of all five datasets together yielded suggestive P values for rs3735520 (P = 9.9 × 10 ) and rs17501108 (P = 9.9 × 10 ). In addition, SNP rs3735520 was found to be associated with serum HGF level in normal individuals (P = 0.036). Conclusions. Taken together, these results implicate genetic variation at the HGF locus with keratoconus susceptibility. © 2011 The Association for Research in Vision and Ophthalmology, Inc.

Do psychosocial factors moderate the association of fixed-term employment with work interference with family and sleeping problems in registered nurses: A cross-sectional questionnaire survey

Background: The use affixed-term employment has increased lately, particularly in Europe and in the health care sector. Previous studies have shown that especially among the health care sector employee's organizational justice perceptions and job control are important factors that are directly related to the welfare and attitudes of employees and may also help to buffer the negative impacts of many detrimental factors.

Association of impulsivity with sleep duration and insomnia in an employee population

Clinical studies have linked impulsivity and insomnia in patients, but little is known about this association in non-clinical settings. This study examined whether impulsive temperament is associated with sleep duration and insomnia complaints in a large cohort of hospital employees (535 men and 4014 women). Linear regression models were related to prospective data from two surveys conducted in 1998 and 2000. Adjustments were made for age, marital status, education, shift work, smoking, alcohol consumption, body mass index, physical activity, minor psychiatric morbidity, social support, somatic disease, depression and other psychiatric disease in 1998. In men, higher impulsivity predicted shorter sleep duration and waking up several times per night independent of baseline characteristics. In women, higher impulsivity predicted having difficulty falling asleep and waking up feeling tired after the usual amount of sleep after adjustment for most of covariates. However, these associations turned out to be non-significant after adjustment for somatic and psychiatric disease. These results support the hypothesis that impulsive temperament could be a risk factor for insomnia in men. (c) 2007 Elsevier Ltd. All rights reserved.

On the association of ULXs with young superclusters: M82 X-1 and a new candidate in NGC 7479

We investigate the spatial coincidence of ultraluminous X-ray sources (ULXs) with young massive stellar clusters. In particular, we perform astrometry on Chandra and Hubble Space Telescope (HST) data of two ULXs that are possibly associated with such clusters.

The Association of Ownership Type With Job Insecurity and Worry About Job Stability The Moderating Effects of Fair Management, Positive Leadership, and Employment Type

This study examined whether the ownership type is associated with job insecurity and worry about job stability and whether the type of employment contract, positive leadership, and fair management moderated these associations. Survey data from 1249 Finnish female elderly care staff aged 18 to 69 years were used. Job insecurity and worry about job stability were highest in not-for-profit sheltered homes. However, positive leadership and fair management were able to mitigate this insecurity and worry. Job insecurity was highest among fixed-term employees in public sheltered homes or not-for-profit nursing homes. Thus, promoting good leadership and fair management would be of importance.