CSF ubiquitin as a specific biomarker in Alzheimer's disease.

Alzheimer's disease (AD) is the most common cause of dementia worldwide. Although, many putative biomarkers are reported for AD, only a few have been validated in the clinical setting. Ubiquitin levels increase in cerebrospinal fluid (CSF) of patients with AD, but its diagnostic value is not clear. In this present study we evaluate the performance of ubiquitin as a diagnostic marker and deduce a statistical association with disease pathology in AD. Ubiquitin levels were estimated in subjects with AD, other forms of dementias, neurological disorders and healthy age matched population. The levels of ubiquitin were significantly higher in subjects with AD when compared with other groups (p<0.0001). A significant positive correlation was observed between ubiquitin, tau and apolipoprotein Eε4 genotype; with Aß42 the correlation was negative. By comparing the effect size of the association between ubiquitin and a diagnosis of AD, we find that high ubiquitin levels are specific for AD. We obtained an odds ratio of 5.6 (95% CI 5.0-7.7) for ubiquitin, towards a diagnosis of AD based on clinical criteria, CSF biomarker signature (Aß42+tau) and apolipoprotein Eε4 genotype. Hence, all our findings taken together provide a strong statistical association linking ubiquitin to the pathology in AD. We also find that, the performance of ubiquitin as a diagnostic marker is comparable to that of CSF Aß42 or tau or apolipoprotein Eε4 genotype considered individually.

Association between apolipoprotein E genotype and cancer susceptibility: a meta-analysis.

BACKGROUND: Apolipoprotein E (ApoE), a protein primarily involved in lipoprotein metabolism, occurs in three isoforms (E2, E3 and E4). Studies evaluating the association between APOE genotype and incidence of malignancies have given inconclusive results. OBJECTIVE: The objective of the present study was to analyze the association between APOE genotype and incidence of cancer by a meta-analysis. METHODS: We conducted a literature search in the electronic databases for studies with information on APOE genotype in malignancies. Sixteen studies (14 case-control and 2 cohort; 77,970 controls and 12,010 cases) were included for the present meta-analysis. Pooled odds ratios (OR) with 95 % confidence intervals (CI) were calculated assuming a random-effect model for all the genotypes and alleles. Subgroup analyses based on study design, ethnicity of populations, site of cancer and source of controls were performed as a post hoc measure. Appropriate tests to detect heterogeneity, publication bias and sensitivity were done at all stages. The review protocol is registered with the PROSPERO database vide registration number CRD42013006496. RESULTS: The pooled effect measure for the comparisons did not reveal an association in primary analyses. In the subgroup analyses, we observed a negative association between APOE4+ genotypes and overall risk of cancer in the cohort study subgroup (pooled OR 0.86; 95 % CI 0.82-0.91; p < 0.00001; I (2) = 0 %). Sensitivity analyses did not alter the overall pooled effect measure, and there were no evidences to suggest a publication bias. CONCLUSION: Overall, the present meta-analysis did not show any association between APOE alleles and genotypes with incidence of cancer in general.

Single-nucleotide polymorphisms in Toll-like receptor (TLR)-2, TLR4 and heat shock protein 70 genes and susceptibility to scrub typhus.

Scrub typhus is a highly prevalent bacterial infection in India and South Asia that is caused by Orientia tsutsugamushi. The innate immune response to infections is modulated by Toll-like receptors (TLRs) and heat shock proteins (HSPs). This study was done to assess the prevalence and possible association of TLR and HSP polymorphisms in scrub typhus. TLR4 Asp299Gly, TLR4 Thr399Ile, TLR2 Arg753Gln and HSP70-2 A1267G are single-nucleotide polymorphisms (SNPs) that may modulate their activities, and these SNPs were assessed in 137 scrub typhus patients and 134 controls by PCR restriction fragment length polymorphism. We found that the two TLR4 mutations, TLR4 D299G and TLR4T399I, were present in 19.5% and 22% of the study population, respectively, and was in significant linkage disequilibrium with a D' of 0.8. The TLR2 mutation was found to be rare, whereas the HSP A>G mutation was very common (77.5%). Compared with the controls, the prevalence of heterozygous genotype of the TLR4D299G SNP, but not any of the other SNPs, was significantly higher among scrub typhus patients. Further studies using a larger sample size and more candidate genes may better enable in determining the role of these associations in susceptibility and severity of scrub typhus.