Dataset Information

Immune-related gene polymorphisms in pulmonary diseases.

ABSTRACT: Between the DNA sequences of two randomly-selected human genomes, which consist of over 3 billion base pairs and twenty five thousand genes, there exists only 0.1% variation and 99.9% sequence identity. During the last couple of decades, extensive genome-wide studies have investigated the association between single-nucleotide polymorphisms (SNPs), the most common DNA variations, and susceptibility to various diseases. Because the immune system's primary function is to defend against myriad infectious agents and diseases, the large number of people who escape serious infectious diseases underscores the tremendous success of this system at this task. In fact, out of the third of the global human population infected with Mycobacterium tuberculosis during their lifetime, only a few people develop active disease, and a heavy chain smoker may inexplicably escape all symptoms of chronic obstructive pulmonary disease (COPD), lung cancer, and other smoke-associated lung diseases. This may be attributable to the genetic makeup of the individual(s), including their SNPs, which provide some resistance to the disease. Pattern recognition receptors (PRRs), transcription factors, cytokines and chemokines all play critical roles in orchestrating immune responses and their expression/activation is directly linked to human disease tolerance. Moreover, genetic variations present in the immune-response genes of various ethnicities may explain the huge differences in individual outcomes to various diseases and following exposure to infectious agents. The current review focuses on recent advances in our understanding of pulmonary diseases and the relationship of genetic variations in immune response genes to these conditions.

SUBMITTER: Singh DP

PROVIDER: S-EPMC5464945 | biostudies-literature | 2017 May

REPOSITORIES: biostudies-literature

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Immune-related gene polymorphisms in pulmonary diseases.

Singh Dhirendra P DP Bagam Prathyusha P Sahoo Malaya K MK Batra Sanjay S

Toxicology 20170330

Between the DNA sequences of two randomly-selected human genomes, which consist of over 3 billion base pairs and twenty five thousand genes, there exists only 0.1% variation and 99.9% sequence identity. During the last couple of decades, extensive genome-wide studies have investigated the association between single-nucleotide polymorphisms (SNPs), the most common DNA variations, and susceptibility to various diseases. Because the immune system's primary function is to defend against myriad infec ...[more]

PMID: 28366820

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Project description:BackgroundBecause immune responses are sensitive to environmental changes that drive selection of genetic variants, we hypothesized that polymorphisms of some xenobiotic response and immune response genes may be associated with specific types of immune-mediated diseases (IMD), while others may be associated with IMD as a larger category regardless of specific phenotype or ethnicity.ObjectiveTo examine transethnic gene-IMD associations for single nucleotide polymorphism (SNP) frequencies of prototypic xenobiotic response genes-aryl hydrocarbon receptor (AHR), AHR nuclear translocator (ARNT), AHR repressor (AHRR) - and a prototypic immune response gene, protein tyrosine phosphatase, non-receptor type 22 (PTPN22), in subjects from the Environmental Polymorphisms Registry (EPR).MethodsSubjects (n?=?3731) were genotyped for 14 SNPs associated with functional variants of the AHR, ARNT, AHRR, and PTPN22 genes, and their frequencies were compared among African Americans (n?=?1562), Caucasians (n?=?1838), and Hispanics (n?=?331) with previously reported data. Of those genotyped, 2015 EPR subjects completed a Health and Exposure survey. SNPs were assessed via PLINK for associations with IMD, which included those with autoimmune diseases, allergic disorders, asthma, or idiopathic pulmonary fibrosis. Transethnic meta-analyses were performed using METAL and MANTRA approaches.ResultsARNT SNP rs11204735 was significantly associated with autoimmune disease by transethnic meta-analyses using METAL (odds ratio, OR [95% confidence interval]?=?1.29 [1.08-1.55]) and MANTRA (ORs ranged from 1.29 to 1.30), whereas ARNT SNP rs1889740 showed a significant association with autoimmune disease by METAL (OR?=?1.25 [1.06-1.47]). For Caucasian females, PTPN22 SNP rs2476601 was significantly associated with autoimmune disease by allelic association tests (OR?=?1.99, [1.30-3.04]). In Caucasians and Caucasian males, PTPN22 SNP rs3811021 was significantly associated with IMD (OR?=?1.39 [1.12-1.72] and 1.50 [1.12-2.02], respectively) and allergic disease (OR?=?1.39 [1.12-1.71], and 1.62 [1.19-2.20], respectively). In the transethnic meta-analysis, PTPN22 SNP rs3811021 was significantly implicated in IMD by METAL (OR?=?1.31 [1.10-1.56]), and both METAL and MANTRA suggested that rs3811021 was associated with IMD and allergic disease in males across all three ethnic groups (IMD METAL OR?=?1.50 [1.15-1.95]; IMD MANTRA ORs ranged from 1.47 to 1.50; allergic disease METAL OR?=?1.58 [1.20-2.08]; allergic disease MANTRA ORs ranged from 1.55 to 1.59).ConclusionsSome xenobiotic and immune response gene polymorphisms were shown here, for the first time, to have associations across a broad spectrum of IMD and ethnicities. Our findings also suggest a role for ARNT in the development of autoimmune diseases, implicating environmental factors metabolized by this pathway in pathogenesis. Further studies are needed to confirm these data, assess the implications of these findings, define gene-environment interactions, and explore the mechanisms leading to these increasingly prevalent disorders.

Dataset Information

Immune-related gene polymorphisms in pulmonary diseases.

Publications

Immune-related gene polymorphisms in pulmonary diseases.

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