Variations in host genes encoding adhesion molecules and susceptibility to falciparum malaria in India

<p>Abstract</p> <p>Background</p> <p>Host adhesion molecules play a significant role in the pathogenesis of <it>Plasmodium falciparum </it>malaria and changes in their structure or levels in individuals can influence the outcome of infection. The aim of this study was to investigate the association of SNPs of three adhesion molecule genes, <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36</it>, with severity of falciparum malaria in a malaria-endemic and a non-endemic region of India.</p> <p>Methods</p> <p>The frequency distribution of seven selected SNPs of <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36 </it>was determined in 552 individuals drawn from 24 populations across India. SNP-disease association was analysed in a case-control study format. Genotyping of the population panel was performed by Sequenom mass spectroscopy and patient/control samples were genotyped by SNaPshot method. Haplotypes and linkage disequilibrium (LD) plots were generated using PHASE and Haploview, respectively. Odds-ratio (OR) for risk assessment was estimated using EpiInfo™ version 3.4.</p> <p>Results</p> <p>Association of the ICAM1 rs5498 (exon 6) G allele and the CD36 exon 1a A allele with increased risk of severe malaria was observed (severe versus control, OR = 1.91 and 2.66, P = 0.02 and 0.0012, respectively). The CD36 rs1334512 (-53) T allele as well as the TT genotype associated with protection from severe disease (severe versus control, TT versus GG, OR = 0.37, P = 0.004). Interestingly, a SNP of the <it>PECAM1 </it>gene (rs668, exon 3, C/G) with low minor allele frequency in populations of the endemic region compared to the non-endemic region exhibited differential association with disease in these regions; the G allele was a risk factor for malaria in the endemic region, but exhibited significant association with protection from disease in the non-endemic region.</p> <p>Conclusion</p> <p>The data highlights the significance of variations in the <it>ICAM1</it>, <it>PECAM1 </it>and <it>CD36 </it>genes in the manifestation of falciparum malaria in India. The <it>PECAM1 </it>exon 3 SNP exhibits altered association with disease in the endemic and non-endemic region.</p

Assessment of the Most Feasible Method for the Management of Facial Injuries in Children Without Hampering the Facial Growth: A Hospital Based Prospective Study

Aim: To access the most feasible method for the management of facial injuries in children without hampering the facial growth. Material &amp; Methods: The present study was conducted on 100 child patients with facial injuries attending the outpatient department of dentistry. Results: A total of 120 children were afflicted by facial injuries, the incidence being 3.24%. Among the etiological factors it was evident that fall (45.8%) was the major etiological factor. There was 100% improvement in mouth opening postoperatively treated by both the methods. Conclusion: Most of the mandibular fractures were found in the parasymphysis region. Simple fracture seems to be commonest in the mandible. Most of the mandibular and midface fractures in children were amenable to conservative therapies except a few which required surgical intervention

Distinct cytokine profiles define immune response to falcipatum malaria in region of high and low transmission

The immune effector response to Plasmodium falciparum infection involves a finely-tuned interplay between different cell types and cytokines. However, the processes by which they mediate the development of clinical immunity, in areas of different endemicity, are poorly understood. We analyzed circulating levels of pro-inflammatory (TNF, IFN-γ, IL-12, IL-16) and anti-inflammatory (IL-4, IL-10, IL-13) cytokines in control and patient groups drawn from a P. falciparum-endemic and a non-endemic region of India. The endemic region control population exhibited a lower pro- to anti-inflammatory cytokine ratio, indicating a shift towards a high basal Th2 response. Levels of IL-10 contributed most towards the region-specific difference in basal cytokine response. IL-10 was also the strongest predictor of disease in the endemic region, while IL-12, along with IL-10 and IL-6, contributed most to disease outcome in the non-endemic region. A low, mean IFN-γ/IL-10 ratio was associated with disease severity in the endemic region (p &#60; 0.0001). In contrast, a low mean IL-12/IL-10 ratio correlated with disease outcome in the non-endemic region (p &#60; 0.0001). In the endemic region, IL-13 correlated negatively with IFN-γ in severe patients (Spearman's ρ: -0.49; p : 0.013), while in the non-endemic region, IL-13 correlated negatively with IL-6 in severe malaria patients (Spearman's ρ: -0.485; p : 0.001). In conclusion, levels of pro- and anti-inflammatory cytokines and the relative balance between the Th1 and Th2 response, illustrates how populations residing in areas of varying disease endemicity may respond to P. falciparum-induced immune challenge

Comprehensive SNP Scan of DNA Repair and DNA Damage Response Genes Reveal Multiple Susceptibility Loci Conferring Risk to Tobacco Associated Leukoplakia and Oral Cancer

Polymorphic variants of DNA repair and damage response genes play major role in carcinogenesis. These variants are suspected as predisposition factors to Oral Squamous Cell Carcinoma (OSCC). For identification of susceptible variants affecting OSCC development in Indian population, the ‘‘maximally informative’’ method of SNP selection from HapMap data to non-HapMap populations was applied. Three hundred twenty-five SNPs from 11 key genes involved in double strand break repair, mismatch repair and DNA damage response pathways were genotyped on a total of 373 OSCC, 253 leukoplakia and 535 unrelated control individuals. The significantly associated SNPs were validated in an additional cohort of 144 OSCC patients and 160 controls. The rs12515548 of MSH3 showed significant association with OSCC both in the discovery and validation phases (discovery P-value: 1.43E-05, replication P-value: 4.84E-03). Two SNPs (rs12360870 of MRE11A, P-value: 2.37E-07 and rs7003908 of PRKDC, P-value: 7.99E-05) were found to be significantly associated only with leukoplakia. Stratification of subjects based on amount of tobacco consumption identified SNPs that were associated with either high or low tobacco exposed group. The study reveals a synergism between associated SNPs and lifestyle factors in predisposition to OSCC and leukoplakia

Fundamental cosmological observations and data interpretation

ISBN 978364200791