Continuous admission to primary school and mental health problems

Background: Younger children in a school class have higher rates of mental health problems if admission to primary school occurs once a year. This study examines whether this relative age effect also occurs if children are admitted to school continuously throughout the year. Methods: We assessed mental health problems based on parent-reports (using the Child Behavior Checklist, CBCL) and on professional assessments, among two Dutch national samples of in total 12,221 children aged 5-15 years (response rate: 86.9%). Results: At ages 5-6, we found a higher occurrence of mental health problems in relatively young children, both for mean CBCL scores (p = 0.017) and for problems assessed by child health professionals (p < 0.0001). At ages 7-15, differences by relative age did not reach statistical significance. Conclusion: Continuous admission to primary school does not prevent mental health problems among young children, but may do so at older ages. Its potential for the prevention of mental problems deserves further study

Erythrocyte Inosine triphosphatase activity: A potential biomarker for adverse events during combination antiretroviral therapy for HIV

The purine analogues tenofovir and abacavir are precursors of potential substrates for the enzyme Inosine 5’-triphosphate pyrophosphohydrolase (ITPase). Here, we investigated the association of ITPase activity and ITPA genotype with the occurrence of adverse events (AEs) during combination antiretroviral therapy (cART) for human immunodeficiency virus (HIV) infection. In 393 adult HIV-seropositive patients, AEs were defined as events that led to stop of cART regimen. ITPase activity 4 mmol IMP/mmol Hb/hour was considered as normal. ITPA genotype was determined by testing two ITPA polymorphisms: c.94C>A (p. Pro32Thr, rs1127354) and c.124+21A>C (rs7270101). Logistic regression analysis determined odds ratios for developing AEs. In tenofovir-containing regimens decreased ITPase activity was associated with less AEs (p = 0.01) and longer regimen duration (p = 0.001). In contrast, in abacavir-containing regimens decreased ITPase activity was associated with more AEs (crude p = 0.02) and increased switching of medication due to AEs (p = 0.03). ITPA genotype wt/wt was significantly associated with an increase in the occurrence of AEs in tenofovir-containing regimens. Decreased ITPase activity seems to be protective against occurrence of AEs in tenofovir-containing cART, while it is associated with an increase in AEs in abacavir-containing regimens

Facioscapulohumeral muscular dystrophy: reproductive counseling, pregnancy, and delivery in a complex multigenetic disease

Reproductive counseling in facioscapulohumeral muscular dystrophy (FSHD) can be challenging due to the complexity of its underlying genetic mechanisms and due to incomplete penetrance of the disease. Full understanding of the genetic causes and potential inheritance patterns of both distinct FSHD types is essential: FSHD1 is an autosomal dominantly inherited repeat disorder, whereas FSHD2 is a digenic disorder. This has become even more relevant now that prenatal diagnosis and preimplantation genetic diagnosis options are available for FSHD1. Pregnancy and delivery outcomes in FSHD are usually favorable, but clinicians should be aware of the risks. We aim to provide clinicians with case-based strategies for reproductive counseling in FSHD, as well as recommendations for pregnancy and delivery.Genetics of disease, diagnosis and treatmen

Risk factors for drug-induced long QT syndrome

Congenital long-QT syndrome (cLQTS) is a ventricular arrhythmia that is characterised by a prolonged QT interval on the surface electro-cardiogram (ECG). Clinical symptoms include sudden loss of consciousness (syncopes), seizures, cardiac arrest and sudden death. The prevalence of this inherited disease is approximately one in 10,000 in Caucasians. Over the last decade, more than 200 different diseases causing mutations have been identified in five genes that encode ion channels involved in the delicate balance of inward and outward K/Ca currents during the cardiac action potential. A prolonged QT interval accompanied by very similar clinical symptoms as in cLQTS can also occur in otherwise healthy individuals after the intake of specific drug(s). This phenomenon is known as 'acquired' or 'drug-induced' long-QT syndrome. Because the clinical symptoms of the two forms are very similar, the question arises whether a common underlying genetic basis also exists. Several studies indicate that only a minority (approximately 10%) of the drug-induced LQTS cases can be explained by a mutation or polymorphism in one of the known LQTS genes. Even though the disease can often at least partially be explained by environmental factors, mutations or polymorphisms in other genes are also expected to be involved, including genes encoding drug-metabolising enzymes, adrenergic receptors, hormone-related genes and mitochondrial genes. This article reviews the current knowledge on risk factors for drug-induced LQTS, with a special emphasis on the role of genetic determinants

Fruit consumption reduces the effect of smoking on bladder cancer risk. The Belgian case control study on bladder cancer

We have hypothesized that consumption of fruit and vegetables may be associated with reduced risk of bladder cancer and that this may interact with cigarette smoking and metabolic genetic polymorphisms. A population-based case-control study was performed in the Belgian province of Limburg among 200 cases and 385 controls. Logistic regression was performed to calculate odds ratios (ORs) for bladder cancer occurrence with corresponding 95% confidence intervals (95% CI). Effect modification by smoking was investigated. We also evaluated interaction between fruit intake and GSTM1, GSTT1, NAT2 and SULT1A1 amongst "ever-smokers." Total vegetable intake was not significantly associated with the risk of bladder cancer (OR 1.15, 95% CI: 0.70-1.88 for the highest compared to the lowest tertile). However, total fruit intake was negatively associated with bladder cancer risk (OR 0.61, 95% CI 0.37-0.99 comparing the same tertiles). Among individuals with low daily fruit consumption, ever smokers had a highly increased risk of bladder cancer risk (OR: 4.23, 95% CI: 1.91-9.40). By increasing the daily fruit consumption, the risk of "ever-smokers" for developing bladder cancer decreased, however it remained significant (OR: 2.15; 95CI%: 1.15-4.05). No interaction was identified between the different genotypes and fruit consumption. We conclude that fruit consumption may decrease the effect of smoking on developing bladder cancer. Antioxidants, found in fruit, may protect against the damage caused by free radicals found in cigarette smoke. Metabolic polymorphisms appear not to modify this relation. (c) 2005 Wiley-Liss, Inc

Does occupational exposure to PAHs, diesel and aromatic amines interact with smoking and metabolic genetic polymorphisms to increase the risk on bladder cancer?; The Belgian case control study on bladder cancer risk

To investigate the association between occupational exposure to polycyclic aromatic hydrocarbons, aromatic amines and diesel and bladder cancer risk and the modification by smoking and metabolic polymorphisms, have we recruited 200 cases and 385 population controls. The adjusted OR of bladder cancer was 5.75 (95%CI 2.09-15.83) comparing the highest tertile of the cumulative probability of occupational exposure to aromatic amines with no occupational exposure. A possible interaction between occupational exposures to aromatic amines and smoking was found. The increased ORs of GSTM1, GSTT1, NAT2 and SULT1A1 among those ever occupational exposed was explored by estimating the false-positive report probability. We confirm that occupational exposure to aromatic amines is associated with an increase in bladder cancer ris

A single hERG mutation underlying a spectrum of acquired and congenital long QT syndrome phenotypes

The long QT syndrome (LQTS) is a multi-factorial disorder that predisposes to life-threatening arrhythmias. Both hereditary and acquired subforms have been identified. Here, we present clinical and biophysical evidence that the hERG mutation c.1039 C>T (p.Pro347Ser or P347S) is responsible for both the acquired and the congenital phenotype. In one case the genotype remained silent for years until the administration of several QT-prolonging drugs resulted into a full-blown phenotype, that was reversible upon cessation of these compounds. On the other hand the mutation was responsible for a symptomatic congenital LQTS in a Dutch family, displaying a substantial heterogeneity of the clinical symptoms. Biophysical characterization of the p.Pro347Ser potassium channels using whole-cell patch clamp experiments revealed a novel pathogenic mechanism of reciprocal changes in the inactivation kinetics combined with a dominant-negative reduction of the functional expression in the heterozygous situation, yielding a modest genetic predisposition for LQTS. Our data show that in the context of the multi-factorial aetiology underlying LQTS a modest reduction of the repolarizing power can give rise to a spectrum of phenotypes originating from one mutation. This observation increases the complexity of genotype-phenotype correlations in more lenient manifestations of the disease and underscores the difficulty of predicting the expressivity of the LQTS especially for mutations with a more subtle impact such as p.Pro347Ser

Genetics of maximally attained lung function: A role for leptin?

SummaryObjectivesTo estimate the heritabilities of maximally attained lung function in young adult twins, and to examine whether circulating leptin, leptin (LEP) and leptin receptor (LEPR) gene polymorphisms are associated with maximally attained lung function.MethodsMeasures on forced expiratory volume in 1 s (FEV1) and forced vital capacity (FVC) were available of 578 twins recruited from the East Flanders Prospective Twin Survey (165 monozygotic (MZ) and 73 dizygotic (DZ) complete pairs and 102 single twins). Twin model fitting and (genetic) association analyses were performed.ResultsIntra-pair correlations of FEV1 and FVC did not differ significantly between MZ monochorionic and MZ dichorionic pairs. Heritability estimates of FEV1 and FVC were 69% and 63%, respectively. The A allele of the LEP 19G>A SNP was significantly associated with a lower FEV1 (pAdditive = 0.01) and FVC (pDominant = 0.047), while the LEPR K109R and Q223R SNPs showed no associations. Accounting for body mass index, serum leptin was negatively associated with FVC (p = 0.02) in men, but not in women.ConclusionsMore than 60% of variation in maximally attained FEV1 and FVC is explained by genetic factors. Moreover, these results suggest that leptin may be important in the determination of maximally attainable lung function