Vitamin D receptor polymorphisms and diseases.

Tuberculosis (TB) is a leading cause worldwide of human mortality attributable to a single infectious agent. Recent studies targeting candidate genes and "case-control" association have revealed numerous polymorphisms implicated in host susceptibility to TB. Here, we review current progress in the understanding of causative polymorphisms in host innate immune genes associated with TB pathogenesis. We discuss genes encoding several types of proteins: macrophage receptors, such as the mannose receptor (MR, CD206), dendritic cell-specific ICAM-3-grabbing nonintegrin (DC-SIGN, CD209), Dectin-1, Toll-like receptors (TLRs), complement receptor 3 (CR3, CD11b/CD18), nucleotide oligomerization domain 1 (NOD1) and NOD2, CD14, P2X7, and the vitamin D nuclear receptor (VDR); soluble C-type lectins, such as surfactant protein-A (SP-A), SP-D, and mannose-binding lectin (MBL); phagocyte cytokines, such as tumor necrosis factor (TNF), interleukin-1β (IL-1β), IL-6, IL-10, IL-12, and IL-18; chemokines, such as IL-8, monocyte chemoattractant protein 1 (MCP-1), RANTES, and CXCL10; and other important innate immune molecules, such as inducible nitric oxide synthase (iNOS) and solute carrier protein 11A1 (SLC11A1). Polymorphisms in these genes have been variably associated with susceptibility to TB among different populations. This apparent variability is probably accounted for by evolutionary selection pressure as a result of long-term host-pathogen interactions in certain regions or populations and, in part, by lack of proper study design and limited knowledge of molecular and functional effects of the implicated genetic variants. Finally, we discuss genomic technologies that hold promise for resolving questions regarding the evolutionary paths of the human genome, functional effects of polymorphisms, and corollary impacts of adaptation on human health, ultimately leading to novel approaches to controlling TB.

pdf/innate-immune-gene-polymorphisms-in-tuberculosis-6perennmfi.pdf

Innate Immune Gene Polymorphisms in Tuberculosis

Human macrophage host defense against Mycobacterium tuberculosis.

Despite the discovery of the tuberculosis (TB) bacillus over 100 years ago and the availability of effective drugs for over 50 years, there remain a number of formidable challenges for controlling Mycobacterium tuberculosis (MTb). Understanding the genetic and immunologic factors that influence human susceptibility could lead to novel insights for vaccine development as well as diagnostic advances to target treatment to those who are at risk for developing active disease. Although a series of studies over the past 50 years suggests that host genetics influences resistance to TB, a comprehensive understanding of which genes and variants are associated with susceptibility is only partially understood. In this article, we review recent advances in our understanding of human variation of the immune system and its effects on macrophage function and influence on MTb susceptibility. We emphasize recent discoveries in human genetic studies and correlate these findings with efforts to understand how these variants alter the molecular and cellular functions that regulate the macrophage response to MTb.

/pdf/mycobacterium-tuberculosis-macrophages-and-the-innate-immune-218e51kcqf.pdf

Mycobacterium tuberculosis, macrophages, and the innate immune response: does common variation matter?

Control of human host immunity to mycobacteria.

OBJECTIF: Explorer le role potentiel des polymorphismes du gene recepteur de vitamine D (VDR) et du gene associe a la resistance naturelle de la proteine 1 macrophagique (NRAMP1) dans la sensibilite a la tuberculose pulmonaire (PTB) dans la population chinoise Han. SCHEMA: Dans une etude cas-controle sans appariement ont ete inclus 120 patients PTB bien definis et 240 controles normaux sans relation avec eux. L'information concernant les facteurs de risque potentiels de la tuberculose pulmonaire a ete colligee grâce a un questionnaire standard. L'analyse utilisant la reaction de polymerase en chaine (PCR) et le test de polymorphisme de longueur des fragments de restriction (RFLP) a porte sur les polymorphismes genetiques du gene VDR (TaqI et FokI) et du gene NRAMP1 (INT4-D543N et 3'UTR). On a pratique une regression logistique inconditionnelle et on a estime les odds ratios ainsi que leurs intervalles de confiance a 95 % (IC) et leurs valeurs P par les methodes de la vraisemblance maximale. RESULTATS: L'analyse univariee a demontre que les homozygotes FokI-ff, et les heterozygotes D543N G/A et 3'UTR TGTG+/del sont plus frequents chez les patients que chez les controles. Les OR bruts ont ete respectivement 2,345 (IC95% 1,222-4,499), 2,590 (IC95% 1,043-6,434) et 1,890 (IC95% 1,171-3,051) par comparaison avec les genotypes courants correspondants. Les valeurs de P ont ete respectivement de 0,033, 0,041 et 0,030. Dans l'analyse multivariee, apres ajustement pour les antecedents d'exposition a la tuberculose et d'une immunisation par le BCG, les ORs ajustes ont ete respectivement 4,625 (IC95% 1,737-12,312), 2,.415 (IC95% 1,079-8,759) et 2,187 (IC95% 1,146-4,175) avec des valeurs de P correspondantes de 0,002, 0,036 et 0,018. Ni l'analyse univariee, ni l'analyse multi-variee n'ont decouvert une association significative entre la maladie et TaqI ou INT4. CONCLUSIONS: Les polymorphismes dans les genes VDR et NRAMP1 sont statistiquement associes a la sensibilite a la tuberculose pulmonaire parmi la population chinoise Han.

VDR and NRAMP1 gene polymorphisms in susceptibility to pulmonary tuberculosis among the Chinese Han population: a case-control study.

Handle everyday research tasks with reliable, citation-backed results

Your personal Research Agent to handle research tasks with citation-backed results

Popular Tasks used by Researchers

How can I help with your research?

Meet SciSpace

Get more enhanced response by uploading the PDFs you want me to reference.

No relevant PDFs in your library

SciSpace is the AI research assistant for academics. Run systematic literature reviews on 280M+ papers, and write papers with cited sources. Trusted by 1M+ students, PhDs & researchers.

SciSpace | AI for Research

Analyze PDFs

Code & Manuscripts

Funding & Grants

Literature & Patents

Medical & Clinical Data

Systematic Review

Visualize & Present

Web & Data

Build a Google Scholar-like website for your research.

Build a website

Create charts and images for your research

Create a Chart

Write a paper for submission to a journal

Draft a manuscript

Patent Search

Design eye-catching scientific posters in minutes.

Scientific Poster Generation

Systematic Literature Review

One task is running at the moment. Your messages will be shown right after.

Drag and drop or click here to browse

Loved by <highlight>1 million+</highlight> researchers

Extract a list of specific topics and their sources from unstructured text

Topics

Compare and analyze relevant papers that matches with your search

Papers

Get insights from PDFs and bookmarked papers from your library

My library

Recent searches

Try searching for:

Catch AI-generated content in scholarly and non-scholarly content

{ai} Detector

Ai Writer

Get PDF Summaries, highlighted text explanations 

Chat with PDF

Effortlessly create in-text citations and bibliographies in APA and 2,500 other formats

Citation generator

Get explanations, summaries, and answers on academic papers

Ease up your research workflow with {scispace}'s cohort of exciting AI tools

Elevate your academic writing skills and convey your ideas the way you want

Paraphraser

Explore our range of reading and writing tools

Your file is being prepared and should be ready in a few minutes. If it's a large file, it might take a bit longer. You can close this window, and we'll email you the file when it's done.

You have reached a maximum limit of <strong>{limit}</strong> columns in the table. Remove at least <strong>1</strong> column to add or create another one.

C Z Li

Author Tools

Chat about Author

Papers

VDR and NRAMP1 gene polymorphisms in susceptibility to pulmonary tuberculosis among the Chinese Han population: a case-control study.