ABSTRACT
[This corrects the article DOI: 10.1371/journal.pgen.1007785.].
ABSTRACT
From genomic association studies, quantitative trait loci analysis, and epigenomic mapping, it is evident that significant efforts are necessary to define genetic-epigenetic interactions and understand their role in disease susceptibility and progression. For this reason, an analysis of the effects of genetic variation on gene expression and DNA methylation in human placentas at high resolution and whole-genome coverage will have multiple mechanistic and practical implications. By producing and analyzing DNA sequence variation (n = 303), DNA methylation (n = 303) and mRNA expression data (n = 80) from placentas from healthy women, we investigate the regulatory landscape of the human placenta and offer analytical approaches to integrate different types of genomic data and address some potential limitations of current platforms. We distinguish two profiles of interaction between expression and DNA methylation, revealing linear or bimodal effects, reflecting differences in genomic context, transcription factor recruitment, and possibly cell subpopulations. These findings help to clarify the interactions of genetic, epigenetic, and transcriptional regulatory mechanisms in normal human placentas. They also provide strong evidence for genotype-driven modifications of transcription and DNA methylation in normal placentas. In addition to these mechanistic implications, the data and analytical methods presented here will improve the interpretability of genome-wide and epigenome-wide association studies for human traits and diseases that involve placental functions.
Subject(s)
Genetic Variation , Placenta/metabolism , Adolescent , Adult , Binding Sites/genetics , CpG Islands , DNA Methylation/genetics , Epigenesis, Genetic , Female , Gene Expression Profiling , Gene Expression Regulation , Genome, Human , Genome-Wide Association Study , Genotype , Humans , Polymorphism, Single Nucleotide , Pregnancy , Quantitative Trait Loci , Sequence Analysis, DNA , Transcription Factors/genetics , Transcription Factors/metabolism , Young AdultABSTRACT
Multiple myeloma (MM), a malignancy involving plasma cells, disproportionately affects older adults with an average age of diagnosis of about 70 years. Oftentimes, the therapies used in the treatment of MM are associated with a risk for immunotoxicity, lowering the ability of the immune system to fight off opportunistic infections. This is an important relationship for clinicians to realize as the incidence of opportunistic infections in myeloma patients is increasing. As an example, we present a case of a patient with MM who subsequently developed a cryptococcal infection. Our paper will highlight the key details of the case as well as shed light on the importance of understanding the immunodeficiencies in this patient population. We highlight important aspects of the current literature related to MM and relate them to the associated case.
ABSTRACT
Granulomatosis with polyangiitis (GPA) is a systemic small/medium-sized vessel vasculitis, which is a member of the family of antineutrophil cytoplasmic auto-antibody-associated vasculitides. This disorder affects multiple organs as it is a systemic disease, but overlapping with rheumatoid arthritis is extremely rare, with few cases reported in the medical literature. We report a case of a 55-year-old female with a history of rheumatoid arthritis who presented with recurrent upper/lower respiratory tract symptoms that responded poorly to antibiotics. The patient had elevated antiproteinase antibodies, ANCA IgG titer with a cytoplasmic staining pattern, proteinuria, hematuria, chest imaging showing cavitating and non-cavitating masses, and biopsies of lung and nasal tissue confirming the diagnosis of GPA. Our patient was given immunosuppressant therapy and improvement in lab work and clinical symptoms were seen throughout the course of treatment. This case report is unique as GPA usually rarely presents with rheumatoid arthritis (RA), but in this case, the patient had a history of rheumatoid arthritis with a new biopsy-proven GPA. This case report will help future physicians to better diagnose similar cases and help to facilitate clinical recognition and treatment for the same.