Biomedical subjects

DialGene Consortium

Publications and source records attributed to DialGene Consortium.

6 recordsLinked to original sources

PubMedDate not supplied

Genomic medicine, gene polymorphisms, and human biological diversity.

There is considerable variation in the prevalence of comorbid conditions such as malnutrition, inflammation, cardiovascular disease, and bone disease among end-stage renal disease (ESRD) patients on maintenance hemodialysis. Besides traditional risk factors, these differences also arise from variability in genetic factors and gene-environment interactions. Recent publication of the human genome sequence through the Human Genome and Celera projects has provided a major impetus to the field of molecular genetics and genomic medicine. This review provides a broad overview of recent developments in this field, basic information and terminology in common use, and explores the impact of genetic variations or polymorphisms on human biological diversity.

Biodiversity↗

PubMedDate not supplied

Model for gene-environment interaction: the case for dialysis.

Organ complications in end-stage renal disease (ESRD) such as cardiovascular disease, anemia, bone disease, malnutrition, inflammation, and infections occur in many organ systems and are caused by a multitude of underlying disease-, uremia-, and therapy-related factors, and with a wide range of manifestations and severity. Interindividual variability in the pathophysiologic response of the uremic host to environmental factors, including renal replacement therapy, may be governed to a significant degree by genetic susceptibility factors. Specific genes regulate the pathophysiologic responses of organ systems affected by ESRD and can serve as candidate genes for the host-environment interaction. This review summarizes emerging clinical and translational research work in the field of genetic polymorphism of candidate genes and their effects on the development of organ complications in ESRD. Methodologic limitations of the existing published data, the need for large prospective cohort studies, and potential future risks for the use of genomic information in resource allocation are also highlighted.

Cytokines↗

PubMedDate not supplied

Gene polymorphism association studies in dialysis: cardiovascular disease.

Cardiovascular disease (CVD) is the most important cause of morbidity and mortality in dialysis patients. The high prevalence of CVD is due to the cumulative effects of multiple risk factors from the early stages of chronic kidney disease (CKD). Familial predispositions to CVD, CKD, and their respective risk factors are well known, and it is likely that genetic factors determine the interindividual variability in risks for disease. Advances in genomic technology have facilitated the study of genetic variation--most commonly single nucleotide polymorphisms (SNPs) in candidate genes--and their associations with disease. This review examines CVD in dialysis patients as a model of a complex disease, discusses the approach to gene polymorphism association studies, including the roles of gene-environment and gene-gene interactions and provides an overview of available studies.

Cardiovascular Diseases↗

PubMedDate not supplied

Gene polymorphism association studies in dialysis: the nutrition-inflammation axis.

Although traditional risk factors for cardiovascular disease are common in dialysis patients, they alone cannot explain the unacceptably high prevalence of vascular disease in this patient group. Much recent interest has therefore focused on the role of various nontraditional cardiovascular risk factors, such as inflammation, wasting, obesity, vascular calcification, and oxidative stress. In addition, genetic factors such as single nucleotide polymorphisms (SNPs) may significantly influence the immune response, the levels of inflammatory markers and body composition, as well as the prevalence of vascular calcification in this patient group. While genetic variations in the tumor necrosis factor (TNF)-alpha-308 and interleukin (IL)-10 -1082 SNPs seem to be consistently associated with adverse clinical outcome in end-stage renal disease (ESRD) patients, the results regarding genetic variations in the IL-6 gene have been conflicting. To elucidate the respective role of DNA polymorphisms in the IL-6 and C-reactive protein (CRP) genes, as well as genes that encode vascular calcification inhibitors (such as fetuin-A, matrix Gla protein, and osteoprotegerin), sufficiently powered studies are needed in which both the protein product and the specific phenotype are determined. In addition, polymorphisms in genes related to body composition may be excellent candidates for analysis in the ESRD population, since nutritional parameters are strongly associated with adverse events in these patients. It seems conceivable that in the future, prognostic or predictive multigene DNA assays (which allow a simultaneous and rapid assessment of multiple genetic variants) will provide nephrologists with a more precise approach for the identification of "high-risk" ESRD patients and the development of accurate individualized treatment strategies.

Biomarkers↗

PubMedDate not supplied

Gene polymorphism association studies in dialysis: anemia and host immunity.

The typical complications of end-stage renal disease (ESRD) vary in frequency and severity. Whereas anemia of chronic kidney disease might require high doses of exogenous erythropoietin (EPO) in some individuals, others hardly ever need hormone replacement. The same observation can be made for immune defense functions in patients with ESRD. Our understanding of the functional consequences of genetic polymorphisms in a wide array of genes has recently gained momentum. In patients with ESRD, interindividual differences in anemia parameters have been linked in part to genetic polymorphisms. Indeed, although inflammation is an important predictor of the need for EPO, to date a link to cytokine gene polymorphisms has not been established. However, the need for EPO has been linked to polymorphisms in the angiotensin-converting enzyme (ACE) and vitamin D receptor genes. In contrast, in dialysis patients, interindividual variability in host immune responses, including nonspecific (bacterial) and antigen-specific (viral) immune mechanisms has been linked to variations in the interleukin-10 and myeloperoxidase genes as well as variability in human leukocyte antigens (HLAs). In conclusion, the role of genetic polymorphisms in predicting the development and severity of anemia in chronic kidney disease as well as host immune competence is in its infancy and warrants further inquiry.

Anemia↗

PubMedDate not supplied

Gene polymorphism association studies in dialysis: bone and mineral metabolism.

Abnormalities in bone and mineral metabolism have a significant impact on morbidity and mortality among patients with end-stage renal disease (ESRD). In addition to confounding environmental factors, genetic susceptibility factors may also influence the occurrence and severity of these abnormalities and account for interindividual variability among patients. Indeed, polymorphisms involving genes of the calcium/parathyroid hormone/calcitriol axis have been associated with bone and mineral metabolism abnormalities. This review summarizes studies involving polymorphisms of candidate genes and their effects on the development of complications related to bone and mineral metabolism abnormalities among patients with ESRD.

Bone Density↗