Identifying rheumatoid arthritis susceptibility genes using high-dimensional methods

Although several genes (including a strong effect in the human leukocyte antigen (HLA) region) and some environmental factors have been implicated to cause susceptibility to rheumatoid arthritis (RA), the etiology of the disease is not completely understood. The ability to screen the entire genome for association to complex diseases has great potential for identifying gene effects. However, the efficiency of gene detection in this situation may be improved by methods specifically designed for high-dimensional data. The aim of this study was to compare how three different statistical approaches, multifactor dimensionality reduction (MDR), random forests (RF), and an omnibus approach, worked in identifying gene effects (including gene-gene interaction) associated with RA. We developed a test set of genes based on previous linkage and association findings and tested all three methods. In the presence of the HLA shared-epitope factor, other genes showed weaker effects. All three methods detected SNPs in PTPN22 and TRAF1-C5 as being important. But we did not detect any new genes in this study. We conclude that the three high-dimensional methods are useful as an initial screening for gene associations to identify promising genes for further modeling and additional replication studies

Helicobacter pylori Seropositivity and Risk of Lung Cancer

Lung cancer is the leading cause of cancer mortality worldwide. Helicobacter pylori (H. pylori) is a risk factor for distal stomach cancer, and a few small studies have suggested that H. pylori may be a potential risk factor for lung cancer. To test this hypothesis, we conducted a study of 350 lung adenocarcinoma cases, 350 squamous cell carcinoma cases, and 700 controls nested within the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study (ATBC) cohort of male Finnish smokers. Controls were one-to-one matched by age and date of baseline serum draw. Using enzyme-linked immunosorbent assays to detect immunoglobulin G antibodies against H. pylori whole-cell and cytotoxin-associated gene (CagA) antigens, we calculated odds ratios (ORs) and 95% confidence intervals (95% CIs) for associations between H. pylori seropositivity and lung cancer risk using conditional logistic regression. H. pylori seropositivity was detected in 79.7% of cases and 78.5% of controls. After adjusting for pack-years and cigarettes smoked per day, H. pylori seropositivity was not associated with either adenocarcinoma (OR: 1.1, 95% CI: 0.75–1.6) or squamous cell carcinoma (OR: 1.1, 95% CI: 0.77–1.7). Results were similar for CagA-negative and CagA-positive H. pylori seropositivity. Despite earlier small studies suggesting that H. pylori may contribute to lung carcinogenesis, H. pylori seropositivity does not appear to be associated with lung cancer

Viral Etiology of Encephalitis in Children in Southern Vietnam: Results of a One-Year Prospective Descriptive Study

Viral encephalitis is associated with high morbidity and mortality in Vietnam. However little is known about the causes of the disease due to a lack of diagnostic facilities in this relatively resource-poor setting. Knowledge about the etiologies and clinical outcome of viral encephalitis is necessary for future design of intervention studies targeted at improvement of clinical management, treatment and prevention of the disease. We report the viral agents, clinical outcome and prognostic factors of mortality of encephalitis in children admitted to a referral hospital for children in southern Vietnam. We show that about one third of the enrolled patients die acutely, and that mortality is independently associated with patient age and Glasgow Coma Scale on admission. Japanese encephalitis, dengue virus and enterovirus (including enterovirus 71) are the major viruses detected in our patients. However, more than half of the patients remain undiagnosed, while mortality in this group is as high as in the diagnosed group. This study will benefit clinicians and public health in terms of clinical management and prevention of childhood encephalitis in Vietnam

A peculiar case of Campylobacter jejuni attenuated aspartate chemosensory mutant, able to cause pathology and inflammation in avian and murine model animals

An attenuated Campylobacter jejuni aspartate chemoreceptor ccaA mutant caused gross pathological changes despite reduced colonisation ability in animal models. In chickens, the pathological changes included connective tissue and thickening of the mesenteric fat, as well as the disintegration of the villus tips in the large intestine, whereas in mice, hepatomegaly occurred between 48–72 hours post infection and persisted for the six days of the time course. In addition, there was a significant change in the levels of IL-12p70 in mice infected with the C. jejuni ccaA mutant. CcaA isogenic mutant was hyper-invasive in cell culture and microscopic examination revealed that it had a “run” bias in its “run-and-tumble” chemotactic behaviour. The mutant cells also exhibited lower level of binding to fucosylated and higher binding to sialylated glycan structures in glycan array analysis. This study highlights the importance of investigating phenotypic changes in C. jejuni, as we have shown that specific mutants can cause pathological changes in the host, despite reduction in colonisation potential

Association of <i>Helicobacter pylori</i> (<i>H. pylori</i>) seropositivity with risk of lung adenocarcinoma and squamous cell carcinoma in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

<p>*N's do not sum to total due to missing values.</p>†<p>Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for baseline pack-years and total number of cigarettes per day.</p>‡<p>Single model for CagA-seropositive and CagA-seronegative versus no <i>H. pylori</i> seropositivity.</p

Characteristics of randomly selected lung adenocarcinoma and squamous cell carcinoma cases and matched cancer-free controls from the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

<p>*Controls matched with cases on age at baseline serum draw and date of baseline serum draw.</p>†<p>BMI = body mass index.</p

Association of <i>Helicobacter pylori</i> (<i>H. pylori</i>) seropositivity with risk of lung adenocarcinoma and squamous cell carcinoma by time to diagnosis in the Alpha-Tocopherol, Beta-Carotene Cancer Prevention Study.

<p>*Odds ratios (ORs) and 95% confidence intervals (CIs) were adjusted for baseline pack-years and total number of cigarettes per day.</p>†<p>Derived from a single model for CagA-seropositive and CagA-seronegative versus no <i>H. pylori</i> seropositivity for all cases diagnosed ≤9 years after baseline blood draw and their paired controls.</p>‡<p>Derived from a single model for CagA-seropositive and CagA-seronegative versus no <i>H. pylori</i> seropositivity for all cases diagnosed >9 years after baseline blood draw and their paired controls.</p