Analysis of HapMap tag-SNPs in dysbindin (DTNBP1) reveals evidence of consistent association with schizophrenia

Dystrobrevin binding protein 1 (DTNBP1), or dysbindin, is thought to be critical in regulating the glutamatergic system. While the dopamine pathway is known to be important in the aetiology of schizophrenia, it seems likely that glutamatergic dysfunction can lead to the development of schizophrenia. DTNBP1 is widely expressed in brain, levels are reduced in brains of schizophrenia patients and a DTNBP1 polymorphism has been associated with reduced brain expression. Despite numerous genetic studies no DTNBP1 polymorphism has been strongly implicated in schizophrenia aetiology. Using a haplotype block-based gene-tagging approach we genotyped 13 SNPs in DTNBP1 to investigate possible associations with DTNBP1 and schizophrenia. Four polymorphisms were found to be significantly associated with schizophrenia. The strongest association was found with an A/C SNP in intron 7 (rs9370822). Homozygotes for the C allele of rs9370822 were more than two and a half times as likely to have schizophrenia compared to controls. The other polymorphisms showed much weaker association and are less likely to be biologically significant. These results suggest that DTNBP1 is a good candidate for schizophrenia risk and rs9370822 is either functionally important or in disequilibrium with a functional SNP, although our observations should be viewed with caution until they are independently replicated.

Analysis of killer immunoglobulin-like receptor genes in ankylosing spondylitis

Objectives: To assess the possible association of killer immunoglobulin-like receptor (KIR) genes, specifically KIR3DL1, KIR3DS1 and KIR3DL2, with ankylosing spondylitis (AS). Methods: 14 KIR genes were genotyped in 200 UK patients with AS and 405 healthy controls using multiplex polymerase chain reaction. Sequence-specific oligonucleotide probes were used to subtype 368 cases with AS and 366 controls for 12 KIR3DL2 alleles. Differences in KIR genotypes and KIR3DL2 allele frequencies were assessed using the χp2p test. Results: KIR3DL1 and KIR3DS1 gene frequencies were very similar in cases with AS and controls (odds ratio = 1.5, 95% confidence interval 0.8 to 3.0, and odds ratio = 1.02, 95% confidence interval 0.2 to 5.3, respectively). KIR3DL2 allele frequencies were not significantly different between cases with AS and controls. Conclusions: Neither the KIR gene content of particular KIR haplotypes nor KIR3DL2 polymorphisms contribute to AS.

Analysis of human immunodeficiency virus type 1 drug resistance in children receiving nucleoside analogue reverse-transcriptase inhibitors plus nevirapine, nelfinavir, or ritonavir (Pediatric AIDS Clinical Trials Group 377)

In Pediatric AIDS Clinical Trials Group 377, antiretroviral therapy-experienced children were randomized to 4 treatment arms that included different combinations of stavudine, lamivudine (3TC), nevirapine (Nvp), nelfinavir (Nfv), and ritonavir (Rtv). Previous treatment with zidovudine (Zdv), didanosine (ddI), or zalcitabine (ddC) was acceptable. Drug resistance ((R)) mutations were assessed before study treatment (baseline) and at virologic failure. Zdv(R), ddI(R), and ddC(R) mutations were detected frequently at baseline but were not associated with virologic failure. Children with drug resistance mutations at baseline had greater reductions in virus load over time than did children who did not. Nvp(R) and 3TC(R) mutations were detected frequently at virologic failure, and Nvp(R) mutations were more common among children receiving 3-drug versus 4-drug Nvp-containing regimens. Children who were maintained on their study regimen after virologic failure accumulated additional Nvp(R) and 3TC(R) mutations plus Rtv(R) and Nfv(R) mutations. However, Rtv(R) and Nfv(R) mutations were detected at unexpectedly low rates.

A cost-outcome description of the septic work-up for bacterial infection in neonates in a tertiary care hospital

Analysis of the septic work-up of 194 neonates at Women's College Hospital, Toronto, showed that the only antepartum condition predicting neonatal sepsis was the mother being on antibiotics. The only postnatal condition predicting sepsis was a maternal postpartum white blood cell count over 11,000. The average cost for tests for a septic work-up in these 194 mother-neonate pairs was $71.48 (Canadian dollars), and the average cost of tests to find a septic case was $1,066.77.

High body mass index is not a barrier to physical activity: Analysis of international rugby players' anthropometric data

Recent data indicate that levels of overweight and obesity are increasing at an alarming rate throughout the world. At a population level (and commonly to assess individual health risk), the prevalence of overweight and obesity is calculated using cut-offs of the Body Mass Index (BMI) derived from height and weight. Similarly, the BMI is also used to classify individuals and to provide a notional indication of potential health risk. It is likely that epidemiologic surveys that are reliant on BMI as a measure of adiposity will overestimate the number of individuals in the overweight (and slightly obese) categories. This tendency to misclassify individuals may be more pronounced in athletic populations or groups in which the proportion of more active individuals is higher. This differential is most pronounced in sports where it is advantageous to have a high BMI (but not necessarily high fatness). To illustrate this point we calculated the BMIs of international professional rugby players from the four teams involved in the semi-finals of the 2003 Rugby Union World Cup. According to the World Health Organisation (WHO) cut-offs for BMI, approximately 65% of the players were classified as overweight and approximately 25% as obese. These findings demonstrate that a high BMI is commonplace (and a potentially desirable attribute for sport performance) in professional rugby players. An unanswered question is what proportion of the wider population, classified as overweight (or obese) according to the BMI, is misclassified according to both fatness and health risk? It is evident that being overweight should not be an obstacle to a physically active lifestyle. Similarly, a reliance on BMI alone may misclassify a number of individuals who might otherwise have been automatically considered fat and/or unfit.