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Results for “Genetic Predisposition to Disease”

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At least 19 recordsLinked to original sources
PubMed2005

C1858T functional variant of PTPN22 gene is not associated with celiac disease genetic predisposition.

Recent findings have demonstrated that the single nucleotide polymorphism 1858C-->T located at the P1 motif of the PTPN22 (protein tyrosine phosphatase nonreceptor 22) gene has functional relevance and is associated with a variety of autoimmune diseases. The aim of this study was to assess the role of the PTPN22 1858C-->T polymorphism in the genetic predisposition to celiac disease (CD). We analyzed a case-control cohort composed by 534 patients with CD and 653 healthy controls and additionally a panel of 271 celiac families. The PTPN22 1858C-->T genotyping was performed by TaqMan 5' allelic discrimination assay. We did not observed any statistically significant deviation after comparing allele and genotypic frequencies of PTPN22 1858C-->T between patients with CD and controls. Accordingly, the familial analysis did not reach statistically significant deviation in the transmission of PTPN22 1858C-->T alleles to the affected offspring. Therefore, our data suggest that the PTPN22 1858 single nucleotide polymorphism has no, or only a negligible, effect on CD susceptibility in this Spanish population.

Autoimmune Diseases↗
PubMed1999

[Hereditary neoplastic diseases (genetic predisposition and cancer syndromes)].

After one decade of molecular genetic studies, little doubt remains that cancer is a genetic disease. While mutations in somatic cells may cause cancer, they don't carry forward to the next generation. In fact, most cancers arise in this way. In some individuals mutations in cancer related genes may be present at the constitutional level, inherited from one of the parents. An individual who carries a mutant allele of an inherited cancer gene has a variable risk of cancer that is influenced by other genetic and non-genetic factors (such as other cellular genes, dietary, lifestyle, and environmental factors). Collectively, the syndromes affect about 1% of cancer patients. During the past decade about 25 different cancer susceptibility genes have been reported to be linked to the known hereditary cancer syndromes. Over the period of the last three to five years, studies of the specific mutations responsible for these syndromes and the cellular signaling pathways disrupted by the mutant proteins have begun to provide unprecedented insights into the molecular origin and pathogenesis of inherited and sporadic forms of cancer. This article reviews the cancer susceptibility genes and cancer syndromes, particularly those associated with common malignancies (breast, prostate and colorectal carcinomas). Results of the mutation analysis in BRCA1 and BRCA2 genes of Hungarian breast/ovarian cancer families will be briefly discussed. These data indicate a strong founder effect for some mutations of BRCA1 gene in Hungary. As a results of recent publicity of discoveries of molecular genetics--particularly those related to common malignancies--due to publicity in the scientific and the lay press awareness and demand for predictive DNA tests have dramatically increased worldwide over the past 3 years. The author, as a member of the Breast Cancer Linkage Consortium, shares the consensus view that genetic testing and genetic counseling for cancer risk together with surveillance and management should for the present be offered only through specialist clinical genetic departments as part of a research evaluation.

DNA, Neoplasm↗
PubMed1999

Understanding probabilistic risk in predisposition genetic testing for Alzheimer disease.

The utility of genetic testing in preventing the onset of conditions such as Alzheimer disease (AD) depends upon categorizing individuals based on their "risk" of illness. Although no strategies to prevent the occurrence of AD have been proven effective, the promise of the new molecular medicine is based on the assumption that those "at risk" can be identified, counseled about their likelihood of developing a disease, and prescribed specific preventive interventions. We suggest that this paradigm of disease prevention through risk stratification has limitations that have not been fully explored. Within the fields of cognitive and health psychology, research has addressed how individuals understand the numeric presentation of uncertain future events; this research often focuses on the "perceptual pathology" of lay people. The uncertainty inherent in the risk estimates themselves is rarely considered, nor has research addressed how those risk estimates are created. There has been limited work to date focused on genetic risk assessment, and little is known about how individual might understand the meaning or consequences of being at genetic risk for AD. An emerging social science critique of concepts of risk in genetic medicine offers a broader perspective, examining the process of producing scientific risk estimates as well as the response of individual patients, such as the experience of embodied risk that is central to genetic testing. Making fully informed choices about genetic testing for AD may prove more difficult than our current model of ethical practice suggests.

Alzheimer Disease↗
PubMed2002

Preimplantation diagnosis for diseases with genetic predisposition and nondisease testing.

Preimplantation genetic diagnosis has become a method of choice in genetic practices. The present experience includes thousands of clinical cases of preimplantation genetic diagnosis, demonstrating the safety, accuracy and reliability of the technique and its clinical relevance for those at-risk couples who cannot accept traditional methods for prenatal diagnosis and termination of pregnancy. Most recently, preimplantation genetic diagnosis has been performed for late-onset disorders, such as genetic predisposition to cancers, Alzhelmer's disease and nondisease testing involving human leukocyte antigen typing, never practiced in prenatal diagnosis. The review of these developments suggests the clinical usefulness of this new approach for avoiding the birth of children with genetic predisposition to cancers and other late-onset disorders, or preimplanation human leukocyte antigen matching to provide the treatment of the affected siblings requiring bone marrow transplantation.

Alzheimer Disease↗
PubMed2000

[Genetic predisposition to cardiovascular diseases].

The development of cardiovascular system disorders depends on both environmental and genetic factors. Precise mechanism by which genetic factors may promote atherosclerotic lesion formation is still under investigation. From multiple candidate genes for cardiovascular disorders the special attention should be paid to that which control synthesis of molecules involved in atherosclerosis process. For now lots of experiments have been done to test specific genes speculated to be crucial for the onset and progression of atherosclerosis, including genes of lipoprotein metabolism, coagulation and fibrinolysis system, renin-angiotensin system and substances influencing the metabolism of arterial wall. Many of them showed the association between tested polymorphisms and pathogenesis of cardiovascular diseases.

Blood Coagulation↗
PubMed2005

HLA associated genetic predisposition to autoimmune diseases: Genes involved and possible mechanisms.

Autoimmune diseases are the result of an interplay between predisposing genes and triggering environmental factors, leading to loss of self-tolerance and an immune-mediated destruction of autologous cells and/or tissues. Genes in the HLA complex are among the strongest predisposing genetic factors. The HLA complex genes primarily involved are most often those encoding the peptide-presenting HLA class I or II molecules. A probable mechanism is preferential presentation by the disease-associated HLA molecules of peptides from autoantigens to T cells. Recent studies have shown, however, that other genes in the HLA complex also contribute. Taken together, available evidence suggests that the HLA complex harbour both disease predisposing genes which are quite specific for some autoimmune diseases (e.g. HLA-B27 for ankylosing spondylitis) and others which may be more common for several diseases. This will be briefly reviewed in the following.

Animals↗
PubMed2003

The interleukin-25 gene located in the inflammatory bowel disease (IBD) 4 region: no association with inflammatory bowel disease.

Genetic predisposition has been suggested to play an important role in the pathogenesis of inflammatory bowel diseases (IBDs). Linkage studies have identified a Crohn's disease susceptibility locus on chromosome 14 (14q11-12; IBD4). Interleukin-25 (IL-25) is a newly identified proinflammatory cytokine that has been shown to promote Th2 responses by inducing cytokines such as IL-4, IL-5 and IL-13. The IL-25 gene is located within this susceptibility region at 14q11.2. As IBDs are characterized by an imbalance of the Th1/Th2 cytokine response, we hypothesized that genetic alterations within the IL-25 gene might contribute to IBD. First, direct sequencing of the coding regions of the IL-25 gene in 40 patients with Crohn's disease or ulcerative colitis revealed only a newly reported polymorphism (c424C/A) in exon 2. Next, the frequency of this polymorphism was further investigated in 151 patients with Crohn's disease, 111 patients with ulcerative colitis, and 119 healthy controls to determine its clinical relevance. The genotypes of the c424C/A polymorphism did not reveal any significant differences between patients with Crohn's disease or ulcerative colitis and controls. Genoytype-phenotype relations in patients with Crohn's disease showed a comparable distribution of the c424C/A polymorphism in all subgroups of the Vienna classification. In summary, our data indicate that genetic alterations in the coding regions of the IL-25 gene are unlikely to play a role in IBDs, but the c424C/A polymorphism in the IL-25 gene should be investigated for a potential association with other chronic inflammatory and inherited disorders such as autoimmune diseases.

Adolescent↗
PubMed2000

The IL-10 gene is not involved in the predisposition to inflammatory bowel disease.

Although genetic predisposition for inflammatory bowel disease (IBD) is well established, little is known about the accountable genes. The pathogenesis of IBD is characterized by an imbalanced activation of Th1- and Th2-lymphocytes. IL-10 represents an anti-inflammatory cytokine which downregulates the production of Th1-derived cytokines. To evaluate the role of the IL-10 gene in IBD, two polymorphisms in the promoter region (G/A at position -1082 and C/A at position -592) were genotyped in 142 patients with Crohn's disease (CD), 104 patients with ulcerative colitis (UC), and 400 healthy controls. Significant differences were not apparent, neither in the allele frequencies of either polymorphism, nor in the haplotype frequencies. Screening of the coding region of the IL-10 gene by polymerase chain reaction--single strand conformation polymorphism (PCR-SSCP) analysis revealed a rare sequence variation in exon 1 leading to an amino acid exchange (G-->A; G15R) in two patients with CD and five healthy controls. Therefore, polymorphisms of the IL-10 gene are not demonstrably involved in the predisposition of IBD in our cohorts of patients.

Colitis, Ulcerative↗
PubMed2006

The geneticization of diagnostics.

"Geneticization" is a term used to describe the ways in which the science of genetics is influencing society at large and medicine in particular; it has important implications for the process of diagnostics. Because genetic diagnostics produces knowledge about genetic disease and predisposition to disease, it is essentially influenced by these innovations in the disease concept. In this paper, I argue that genetic diagnostics presents new ethical challenges not because the diagnostic process or method in genetic diagnostics is ethically different in kind from traditional medical diagnostics, but because it relies on a neo-ontological concept of disease in a context of genetic reductionism. Geneticization has not produced a radically new concept of disease, however, but has introduced innovations into the classical ontological concept of disease. When this new concept of disease is held in tandem with genetic reductionism, we are led to the absurd conclusion that disease is the very essence of the human being. I argue that neither the neo-ontological concept of disease nor genetic reductionism is necessary for a proper understanding of genetic diagnostics.

Ethics, Medical↗
PubMed2006

HLA class II disease associations in southern Africa.

Southern Africa harbors several population groups representing a diversity of gene pool origins. This provides a unique opportunity to study genetic disease predisposition in these populations against a common environmental background. Human leukocyte antigen (HLA) association studies of these populations could improve knowledge on inter-population variation and HLA-related disease susceptibility. The aim of this paper is to review HLA class II disease associations reported for southern African population groups, compare them with findings in other populations and identify those unique to southern Africa. A number of HLA class II disease associations appear to be unique to southern African populations. These include DRB1*14011 association with insulin-dependent diabetes mellitus susceptibility in the Xhosa and DRB1*10 and DQB1*0302 with rheumatoid arthritis susceptibility in the South African (SA) Indian and SA Coloreds, respectively. A noteworthy similarity in class II disease association was observed among southern African Caucasoid and their European parental populations. Unique HLA class II disease associations observed in southern Africa are consistent with the notion that unique environmental and natural selective factors have resulted in certain ethnic-specific HLA class II disease associations, while common HLA class II disease associations found across different populations support the notion that common diseases are caused by common, ancient alleles present in indigenous African populations.

Africa, Southern↗
PubMed2004

Apoptosis in tissue inflammation and allergic disease.

Genetic predisposition and environmental instructions tune thresholds for the activation, effector functions and lifespan of T cells, other inflammatory cells and resident tissue cells. Defects in apoptosis and peripheral tolerance in T cells define different allergic phenotypes. In individuals with atopic allergic disease, activated allergen-specific T cells expressing high levels of IFN-gamma predominantly undergo apoptosis in the circulation, skewing the immune response to surviving T helper type 2 (Th2) cells. In affected tissues, these cells switch on effector cytokines and induce the activation and apoptosis of epithelial cells. In individuals with non-atopic monoallergic disease, by contrast, a disturbed balance towards allergen-specific Th2 cells instead of T regulatory type 1 (Tr1) cells characterizes the T cell response.

Animals↗
PubMed1998

Type 1 diabetes and prediabetic state in a monozygotic triplet.

Type 1 diabetes mellitus (IDDM) results from a chronic process of autoimmune destruction of beta cells of the Langerhans islets. The presence of autoantibodies (ICA, GADA, anti-IA2, IAA) in serum precedes the clinical onset of the disease. Genetic predisposition for IDDM is connected with HLA, CTLA-4 and insulin gene region. The aim of the study was the genetic and immunological analysis of a triplet. One of them developed Type 1 diabetes mellitus. We analysed HLA class II, CTLA-4 and insulin gene polymorphisms in the whole family. Besides, we investigated immunological status of three brothers. All patients present identical genotype for VNTR loci: D1S80, D17S5 and Apo B, as well as for HLA-DRB1, -DQA1, -DQB1, CTLA-4 gene and all studied insulin gene polymorphisms. That proves their monozigosity. The triplet presents strong genetic predisposition for IDDM. The two patients without overt diabetes have increased levels of ICA, GADA, IA2 and IAA.

Abatacept↗
PubMed2005

Genome-wide SNP association: identification of susceptibility alleles for osteoarthritis.

The successful identification of genes involved in common human disorders is dependent upon availability of informative sample sets, validated marker panels, a high-throughput scoring technology, and a strategy for combining these resources. We have developed a universal platform based on mass spectrometry (MassARRAY) for analyzing nucleic acids with high precision and accuracy. To fuel this technology we have generated more than 100,000 validated assays for single nucleotide polymorphisms (SNPs) covering virtually all known and predicted human genes, and a large DNA sample bank from more than 50,000 consented diseased (case) and healthy (control) individuals. Taking advantage of MassARRAY's capability for quantitative analysis of nucleic acids, allele frequencies are estimated in sample pools containing large numbers of individual DNAs. Comparing frequencies between case and control pools as a first-pass filtering step is a tremendous advantage in throughput and cost over individual genotyping. We have employed this approach in numerous genome-wide association studies to identify genes implicated in common complex diseases, including osteoarthritis (OA). Access to additional patient samples through collaborations allows us to conduct replication studies that validate true disease genes. These discoveries will expand our understanding of genetic disease predisposition, and our capabilities for early diagnosis and improved therapeutic approaches.

Alleles↗