PubMed Health⌕ Search

SEARCH · PubMed Health

Results for “Genetic predisposition”

Explore indexed PubMed citations for clinical trials, systematic reviews and public health research. Read source abstracts and follow each citation to its original PubMed record.

Quote a phrase for an exact phrase match. Source license links do not imply unrestricted reuse.

At least 109 records · Page 6Linked to original sources
PubMed2005

Genetic predisposition to cancer: the consequences of a delayed diagnosis of Gorlin syndrome.

This report outlines a case of Gorlin syndrome, the diagnosis of which was delayed for many years, and raises a number of important issues. These are the spectrum of late radiotherapy effects, particularly after treatment for benign disease, and the importance of considering the possibility of the presence of a genetic syndrome predisposing to cancer in all individuals before starting any treatment. As our knowledge of genetic syndromes expands, this will become increasingly important. Finally, if a genetic predisposition to cancer is suspected, consideration should be given to obtaining a blood sample from the affected patient for DNA storage, particularly if their prognosis is limited. Currently, genetic testing can only be instituted in most families by first obtaining DNA from an individual affected by cancer, as most genetic mutations are unique to a family. If all relatives with cancer have died, then, at this time, genetic testing cannot usually be attempted, unless such samples have previously been stored.

Aged↗
PubMed2004

Genetic predisposition to wheeze following respiratory syncytial virus bronchiolitis.

BACKGROUND: The nature of the association between severe respiratory syncytial virus (RSV) bronchiolitis and subsequent wheezing remains unknown. In a previous study, we showed that genetic variation in the IL-8-promoter region is associated with susceptibility to severe bronchiolitis. OBJECTIVE: The purpose of this study was to assess the association between wheezing post-bronchiolitis and the genetic variant of IL-8 gene. METHODS: We collected data from 134 children who had suffered from bronchiolitis, enrolled in our previous study. The occurrence of wheezing post-bronchiolitis was recorded from a questionnaire sent by post. The association between the genotype and wheezing phenotype was assessed by family-based and case-control approaches. RESULTS: Family-based association showed that the IL-8 variant was transmitted significantly more often than expected in the children who wheezed after the episode of bronchiolitis (transmission=56%, P=0.02). This effect was not observed in the group of children who had bronchiolitis but did not go on to wheeze. Moreover, the variant was significantly more frequent in post-bronchiolitis wheezers compared with the general population (odds ratio=1.6, 95% confidence interval 1.0-2.6). CONCLUSION: These preliminary results suggest that there is a genetic predisposition to wheeze following severe RSV bronchiolitis.

Alleles↗
PubMed1996

Genetic predisposition to lymphomas in mice.

The spontaneous mouse lymphoma is a model of multifactorial genetic disease. It is induced by the endogenous murine leukemia virus (MuLV), whose genome is inherited as a Mendelian dominant trait. Lymphoma development takes place in multiple stages affected by many host genetic and epigenetic factors. An inbred strain SL/Kh with a high incidence of pre-B lymphomas has been established and the genetic predisposition of SL/Kh mice to lymphomas is being studied in the crosses with other inbred strains of mice. In the cross to the NFS/N lacking endogenous MuLV genome, it has been shown that lymphomas are induced by the expression of Emv-11 provirus (Chr. 7), and the types of B-lineage lymphomas are determined by combinations of the host genes, Esl-1 (Chr. 17) and Foc-1 (Chr. 4). Another gene, Tlsm-1 (Chr. 7) that determines the type of lymphomas to be T-lineage, is identified in the cross with AKR/Ms, with a high incidence of T-lymphomas. The role of the thymus in the development of T-lymphomas in the mouse, and the possible relevance of Tlsm-1 in this step, is discussed. The length of the latent period is determined by a gene Lia-1 (Chr. 17). A maternal resistance factor that is a maternal antibody to MuLV transmitted via milk and that epigenetically inhibits MuLV expression in SL/Ni-Eco-, one of subline of SL/NI mice, has been shown. Weak but definitive maternal resistance also operates in SL/Ni-Eco+, a subline lacking the maternal antibody to MuLV. In the latter, there is a recessive resistance gene Nir-1 (Chr. 4). In the cross with MSM/Ms, a wild mice-derived inbred strain, two resistance genes, Msmr-1 (Chr. 17) and Msmr-2 (Chr. 18), have been identified. In SL/Kh, all of these host genetic and epigenetic factors are favorable for lymphoma development. This model offers not only an understanding of the pathogenesis of virus-induced lymphomas but also may provide starting material for the comparative approach to homologous human diseases.

Animals↗
PubMedDate not supplied

[The physiological characteristics of genetic predisposition to catalepsy in rats depending on the stage of selection].

Male rats with a genetic predisposition to cataleptic reactions revealed a reduced motor activity and a diminished activation of mineralocorticoid and testosterone synthesis in response to a mild stress as compared with the Wistar rats. The reactions, however, were exactly opposite in the Wistar rats with signs of cataleptic features. The data obtained suggest that, when creating genetic animal models of human diseases, the initial stages of breeding should correspond to early stages of the disease whereas advanced stages of breeding are similar to later, chronic phases of the disease.

Adrenal Cortex Hormones↗
PubMed1998

A role for genetic predisposition in subglottic stenosis.

We present the development of ASGS in two of three premature male triplets; the affected infants were monozygotic, while the unaffected triplet was dizygotic. All three shared remarkably similar risk factor profiles. There is suggested the existence of a genetic factor or factors which may predispose certain infants to the development of ASGS. The expression of such genetic influence may be expressed through the a priori presence of CSGS or other genetically based mechanisms including abnormal cartilage growth or development, specific patterns of chondral or mucosal injury, the action of specific growth factors, or the effects of autoimmune or inflammatory mediators. We propose that genetic predisposition be considered a possible risk factor in the development of subglottic stenosis.

Genetic Predisposition to Disease↗
PubMed1999

Interaction of genetic predisposition and environmental factors in the pathogenesis of idiopathic orthostatic intolerance.

BACKGROUND: The hemodynamic and autonomic abnormalities in idiopathic orthostatic intolerance (IOI) have been studied extensively. However, the mechanisms underlying these abnormalities are not understood. If genetic predisposition were important in the pathogenesis of IOI, monozygotic twins of patients with IOI should have similar hemodynamic and autonomic abnormalities. METHODS: We studied two patients with IOI and their identical twins. Both siblings in the first twin pair had orthostatic symptoms, significant orthostatic tachycardia, increased plasma norepinephrine levels with standing, and a greater than normal decrease in systolic blood pressure with trimethaphan infusion. RESULTS: Both siblings had a normal response of plasma renin activity to upright posture. In the second twin pair, only one sibling had symptoms of orthostatic intolerance, an orthostatic tachycardia, and raised plasma catecholamines with standing. The affected sibling had inappropriately low plasma renin activity with standing and was 8-fold more sensitive to the pressor effect of phenylephrine than the unaffected sibling. CONCLUSIONS: We conclude that in some patients, IOI seems to be strongly influenced by genetic factors. In others, however, IOI may be mainly caused by nongenetic factors. These findings suggest that IOI is heterogenous, and that both genetic and environmental factors contribute individually or collectively to create the IOI phenotype.

Adult↗
PubMed2004

Nonsyndromic genetic predisposition to aortic dissection: a newly recognized, diagnosable, and preventable occurrence in families.

The major diseases affecting the aorta are aortic aneurysms and dissections, with patients with acute dissections often presenting in the emergency department (ED). Recent studies demonstrate a strong genetic predisposition to thoracic aortic aneurysms and dissections, independent of syndromes traditionally considered to predispose to aortic disease (such as Marfan syndrome). Nonsyndromic familial thoracic aortic aneurysms and dissections are inherited in families as an autosomal dominant disorder and a variable age of onset of the aortic disease. The case reported here illustrates the critical importance of obtaining a family history of thoracic aortic aneurysms and dissections, along with unexplained sudden death, when assessing an individual with chest pain in the ED, regardless of age and in the absence of a known genetic syndrome.

Adult↗
PubMed1984

Genetic predisposition to cancer.

A minor fraction of cancer occurs in persons who have strong dominantly transmissible genetic predisposition. Retinoblastoma and Wilms' tumor are the most thoroughly studied examples. Hereditary cases involve mutations at the same chromosomal sites. In most carriers of mutation the change cannot be visualized; in some, it is a visible deletion. A significant fraction of nonhereditary cases involve deletion at the same site in tumor cells only, suggesting that mutation at this site is necessary for the initiation of tumor, whether hereditary or not. This may be a general model for human cancer. The initiating mutation is not sufficient, however, since only rare cells are transformed. A second event may be genetic, such that recessive loss of the gene occurs. A two-event genetic model for a major fraction of human cancers is also compatible with the well-established, age-specific incidence of various cancers.

Bloom Syndrome↗
PubMedDate not supplied

Immunohistochemical study of a chondroitin-6-sulfate in growth plates of broiler chickens with high and low genetic predispositions to tibial dyschondroplasia.

The distribution of a chondroitin-6-sulfate (C6S) epitope, which is a biochemical marker of chondrocyte hypertrophy, was studied in the growth plates of two lines of 3-week-old broiler chickens with low and high genetic predispositions to tibial dyschondroplasia (TD). Ultrathin sections of growth plates from both groups were subjected to immunolocalization with monoclonal antibody 3-B-3(-), the epitope of which is increased on proteoglycans made by hypertrophic chondrocytes. Bound antibody was localized with colloidal gold-labeled protein A for observation with an electron microscope. The 3-B-3(-) epitope was localized in pericellular and interterritorial matrix of growth plates of both lines. In the low-TD-incidence birds, the concentration of 3-B-3(-) bound to C6S progressively increased from the proliferative zone to the hypertrophic zone. However, in the high-TD-incidence line, the epitope expression remained at a low level in all zones. The increase of the 3-B-3(-) epitope produced by maturing growth-plate chondrocytes is indicative of changes in the glycosaminoglycan chains of proteoglycans that may be important in the process of matrical calcification. Thus, failure of chondrocytes of the high-TD-incidence line to produce this change in post-translational modification of their proteoglycans could be important in the pathological process.

Animals↗
PubMed2001

Genetic predisposition and the development of posttraumatic stress disorder in an animal model.

BACKGROUND: Exposure to extremely stressful events can lead to Posttraumatic stress disorder (PTSD). Due to the complexity of PTSD, animal models have been designed and advanced to address the role of psychosocial stressors in the etiology; however, the apparent role of genetics in susceptibility to PTSD-like behaviors in animals remains unexplored. METHODS: An animal model of congenital learned helpless (cLH) behavior has been used to study the effects of genetic disposition as a risk factor for the development of PTSD-like behaviors. Animals were monitored for changes in pain tolerance, spatial memory and hypothalamic-pituitary-adrenal functioning after re-exposure to intermittent stress in the presence and absence of situational cues. RESULTS: Exposure to stress resulted in an increase in pain tolerance in the cLH animals. In the spatial memory test 80% of the cLH animals manifested a decrease in performance after exposure to stress. These animals also had a blunted poststress corticosterone response. CONCLUSIONS: The genetic learned helpless animal model exhibited physiologic symptoms of analgesia, cognitive deficits and hyporesponsivity of the hypothalamic-pituitary-adrenal axis similar to those observed in human subjects with PTSD. It is proposed that the cLH model may be a valuable tool for exploring the role of genetic predisposition in the etiology of PTSD.

Animals↗
PubMed2001

[Association of 16189 variant (T-->C transition) of mitochondrial DNA with genetic predisposition to type 2 diabetes in Chinese populations].

OBJECTIVE: To assess the prevalence of 16189 variant (T-->C transition) of mitochondrial DNA in Chinese populations and to study the relation between mtDNA 16189 variant and insulin resistance and the role it plays in genetic predisposition to diabetes. METHODS: PCR and RELP techniques were used to examine 383 unrelated type 2 diabetics and 151 non-diabetic controls selected by random sampling. RESULTS: (1) The prevalence of 16189 variant among type 2 diabetics was significantly higher than that among the controls. (2) The prevalence of 16189 variant was significantly higher among type 2 diabetics with maternal family history than among those without maternal family history. (3) In comparison with the type 2 diabetics without 16189 variant, those with 16189 variant showed higher fasting serum insulin level, decreased insulin sensitivity index, and higher Homa insulin resistance index. (4) In the control group, no significant difference in age, gender, body mass index, waist to hip ratio, serum lipid level, fasting plasma glucose level, fasting serum insulin level, insulin sensitivity index, and Homa insulin resistance index was found between those with 16189 variant and those without 16189 variant. CONCLUSION: 16189 variant of mitochondrial DNA is one of the genetic predisposing factors for type 2 diabetes mellitus in Chinese populations. It might interfere with the energy metabolism and the production of ATP, thus causing insulin resistance in peripheral tissues.

Adenosine Triphosphate↗
PubMed2005

Delayed clearance of fetal lung liquid and sodium transport--genetic predisposition not evident yet.

UNLABELLED: The epithelial Na+ channel (ENaC) contributes to the clearance of fetal lung liquid. In premature infants, low ENaC activity and low expression level of alpha-ENaC have been associated with respiratory failure. The polymorphism in the alpha-ENaC gene remains to be studied as a factor explaining the variation in the incidence of transient tachypnoea or respiratory distress syndrome in the newborn. CONCLUSION: The study of genetic predisposition to common multifactorial diseases requires analyses of large, well-defined cohorts for representative variants of relevant candidate genes.

Epithelial Sodium Channels↗
PubMed2000

Genetic predisposition to breast cancer: a surgical perspective.

BACKGROUND: Molecular alterations in proto-oncogenes, tumour suppressor genes, and genes that function in DNA damage recognition and repair are considered to be hallmarks of a carcinogenic process, including breast carcinogenesis. METHODS: A computer-assisted search of the English literature (Medline database, 1990-1999) was performed, followed by a manual search of the reference list of pertinent articles retrieved. RESULTS: Hereditary breast cancer accounts for 5-10 per cent of all breast cancer cases. About 90 per cent of hereditary breast cancers involve mutation of the BRCA1 and/or BRCA2 genes. Other cancer-related genes (including myc, c-erbB2, Tsg101 and Mdgi) are involved in breast carcinogenesis, but they do not give rise to familial breast cancer syndromes. Risk estimation is the most important clinical implication. Management options for the high-risk mutation carriers include cancer surveillance and preventive strategies (prophylactic surgery or chemoprevention). CONCLUSION: Despite inadequate knowledge about the genetic predisposition to breast cancer and its clinical implications, the demand for genetic testing is likely to expand rapidly. In addition to risk estimation, cancer surveillance and preventive strategies, gene therapy offers a new and theoretically attractive approach to breast cancer management.

BRCA2 Protein↗
PubMed2005

Genetic predisposition for a compromised immune system after multiple trauma.

Severe trauma induces sustained changes of the immune response, which are thought to be related to secondary organ dysfunction. Despite a similar injury severity, the extent of the inflammatory response may vary between polytraumatized patients. It is unclear whether inflammatory variability is associated with genetic variations. In this prospective cohort study, patients were included when the following criteria were fulfilled: Injury Severity Score >16, age 18 to 60 years, and a survival >48 h after injury. Four different polymorphisms (TNF-Nco1, IL-1-Taq1, IL-6-174G/C, and IL-8-251A/T) were determined. Patients were separated according to the severity of the systemic inflammatory response syndrome (SIRS; ACCP/SCCM criteria: >2 criteria at 2 consecutive days or at 3 days of the observation period: group +SIRS; <or=2 criteria: group -SIRS). Ninety-seven severely injured patients were included (-SIRS, 56 patients; +SIRS, 41 patients). A significantly higher incidence of the IL-6-174G allele and the IL-6-174G homozygous genotype in +SIRS patients was observed. The IL-6-174G/C polymorphism was associated with the severity of posttraumatic SIRS. This data points toward a genetic predisposition regarding an enhanced inflammatory response after polytrauma that may be associated with adverse outcome.

Adolescent↗
PubMed2025

Genetic Predisposition to Low-Density Lipoprotein Cholesterol and Incident Type 2 Diabetes.

IMPORTANCE: Treatment to lower high levels of low-density lipoprotein cholesterol (LDL-C) reduces incident coronary artery disease (CAD) risk but modestly increases the risk for incident type 2 diabetes (T2D). The extent to which genetic factors across the cholesterol spectrum are associated with incident T2D is not well understood. OBJECTIVE: To investigate the association of genetic predisposition to increased LDL-C levels with incident T2D risk. DESIGN, SETTING, AND PARTICIPANTS: In this large prospective, population-based cohort study, UK Biobank participants who underwent whole-exome sequencing and genome-wide genotyping were included. Participants were separated into 7 groups with familial hypercholesterolemia (FH), predicted loss of function (pLOF) in APOB or PCSK9 variants, and LDL-C polygenic risk score (PRS) quintiles. Data were collected between 2006 and 2010, with a median follow-up of 13.7 (IQR, 12.9-14.5) years. Data were analyzed from March 1 to November 1, 2024. EXPOSURES: LDL-C level, LDL-C PRS, FH, or pLOF variant status. MAIN OUTCOMES AND MEASURES: Cox proportional hazards regression models adjusted for age, sex, genotyping array, lipid-lowering medication use, and the first 10 genetic principal components were fitted to assess the association between LDL-C genetic factors and incident T2D and CAD risks. RESULTS: Among the 361&#x202f;082 participants, mean (SD) age was 56.8 (8.0) years, 194&#x202f;751 (53.9%) were female, and mean (SD) baseline LDL-C level was 138.0 (33.6) mg/dL. During the follow-up period, 22 619 (6.3%) participants developed incident T2D and 17 966 (5.0%) developed incident CAD. The hazard ratio for incident T2D was lowest in the FH group (0.65; 95% CI, 0.54-0.77), while the highest risk was in the pLOF group (1.48; 95% CI, 1.18-1.86). The association between LDL-C PRS and incident T2D was 0.72 (95% CI, 0.66-0.79) for very high LDL-C PRS, 0.87 (95% CI, 0.84-0.90) for high LDL-C PRS, 1.13 (95% CI, 1.09-1.17) for low LDL-C PRS, and 1.26 (95% CI, 1.15-1.38) for very low LDL-C PRS. CAD risk increased directly with the LDL-C PRS. CONCLUSIONS AND RELEVANCE: In this cohort study, LDL-C and T2D risks were inversely associated across genetic mechanisms for LDL-C variation. Further elucidation of the mechanisms associating low LDL-C risk with increased risk of T2D is warranted.

Humans↗
PubMed2001

Involvement of cAMP- and Ca(2+)/calmodulin-dependent neuronal protein phosphorylation in mechanisms underlying genetic predisposition to audiogenic seizures in rats.

It was shown that increased excitability in neurons underlying epilepsies would be maintained by abnormalities in protein phosphorylation systems. This study was initiated to compare the functioning of Ca(2+)/calmodulin- and cAMP-dependent systems of protein phosphorylation in homogenates of neocortex and hippocampus in three animal groups: genetically prone to audiogenic seizures (GPAS) rats, GPAS rats exposed to daily repeated audiogenic seizures (AGPAS rats) and nonepileptic Wistar ones. We found significant differences in phosphorylation of 270, 58, 54 and 42 kDa proteins in neocortex and hippocampus of GPAS rats in comparison with Wistar ones. Daily repeated seizures induced further modifications of phosphorylation of these proteins in only hippocampus of AGPAS rats as compared with GPAS ones. Ca(2+)-independent, functional CAMKII activity was considerably increased in hippocampus but decreased in neocortex of GPAS rats in comparison with Wistar ones. The activity of PKA was increased both in neocortex and hippocampus of GPAS rats. Daily repeated audiogenic seizures induced the decrease of Ca(2+)-independent CAMKII activity in hippocampus and the increase of PKA activity in neocortex of AGPAS rats in comparison with GPAS ones. The present results indicate that modification of 270, 58, 54, and 42 kDa proteins phosphorylation as well as altered CAMKII and PKA activities might be involved in mechanisms of genetic predisposition to audiogenic seizures.

Acoustic Stimulation↗
PubMed1997

Presymptomatic and predisposition genetic testing: ethical and social considerations.

OBJECTIVE: To provide an overview of the ethical and social concerns that are raised by the use of new genetic tests in asymptomatic persons. DATA SOURCES: Review articles, research studies and legislation related to genetic testing. CONCLUSIONS: Predisposition and presymptomatic testing is possible to any age for adult onset disorders if a mutation is known. Testing without early effective interventions is controversial, especially prenatally and in children. Issues of privacy, discrimination, stigmatization and emotional stress are potential problems. Informed consent is essential before deciding to test. Awareness of the implications of testing can enhance the nurse's advocacy role. IMPLICATIONS FOR NURSING PRACTICE: More studies are necessary to identify the impact of presymptomatic testing on adults and children. Nursing research to identify the family concerns, and to develop effective educational, counseling, and supportive interventions would make a valuable contribution.

Adult↗