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Results for “Genetic susceptibility”

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At least 19 recordsLinked to original sources
PubMed2002

Worry and attitude of men in at-risk families for prostate cancer about genetic susceptibility and genetic testing.

BACKGROUND: The aim of this study was to evaluate worry about genetic susceptibility and the attitude of men with family history of prostate cancer (CaP) toward genetic testing. METHODS: Three hundred seventy-five eligible first-degree relatives (FDR) of men with CaP, were asked to participate in a screening and to fill out a survey covering the worry about genetic susceptibility and interest in genetic testing. RESULTS: Of the 375 candidates contacted, 277 completed the survey, and had undergone PSA measurement. Sixty-four percent worried a little or not at all about inherited predisposition to CaP, while the remainder worried a lot or extremely. The candidates who worried a lot or extremely were men with high levels of durable anxiety disposition (STAI trait), who had undergone a previous screening procedure and men with sons. Ninety-eight percent of men expressed their interest in undergoing genetic testing. The most motivated candidates to have the test done were men with several relatives with CaP. CONCLUSIONS: The level of worry about genetic susceptibility was low and there was a concrete interest in genetic testing in FDR of men with CaP. This interest increased with the number of CaP in the family.

Adult↗
PubMed2005

Mycobacterium avium subsp. paratuberculosis, genetic susceptibility to Crohn's disease, and Sardinians: the way ahead.

The present study was performed to determine what proportion of people in Sardinia with or without Crohn's disease were infected with Mycobacterium avium subspecies paratuberculosis and had a preponderance of allelic variants of Nod 2, an intracellular protein involved in Crohn's disease susceptibility. Genetic analysis of the alleles of the NOD 2/CARD 15 gene (ins C 3020, G 908 R, and R 702 W alleles), linked to susceptibility or genetic predisposition to Crohn's disease in humans, was carried out on specimens from 37 Crohn's disease patients and 34 patients without Crohn's disease. Our results show that more than 70 percent of people in Sardinia with Crohn's disease carry at least one of the susceptibility-associated NOD 2/CARD 15 alleles and were infected with Mycobacterium avium subspecies paratuberculosis.

Crohn Disease↗
PubMed1981

Effect of adrenalectomy on sound-induced seizure susceptibility and intensity in genetically susceptible rats.

Neither seizures susceptibility nor intensity was altered by sham-operation or by adrenalectomy in adult rats that are genetically susceptible to sound-induced seizures. Thus, sound-induced seizures in genetically susceptible rats are analogous to those in genetically susceptible mice to the extent that removal of the adrenal glands does not alter established seizure characteristics in either species.

Acoustic Stimulation↗
PubMed1998

[Genetic susceptibility to multiple sclerosis (MS). INSERM Network of Clinical Research on the Genetic Susceptibility to MS].

The clinical manifestations and neuropathological signs of Multiple Sclerosis (MS) have been known for more than a century, but the cause of MS remains unknown. Epidemiological studies indicate that MS is a multi-factorial disease implicating both environmental factors and genetic susceptibility. The role of HLA in the genetic susceptibility to MS has been known since the seventies. Advances in human genetics now allow a systematic approach to genetic susceptibility in MS: possible strategies are reviewed.

Genetic Predisposition to Disease↗
PubMed2002

Perinuclear neutrophil antibodies are not markers for genetic susceptibility or indicators of genetic heterogeneity in familial ulcerative colitis.

OBJECTIVES: Autoantibodies that bind to the perinuclear region of neutrophils have been suggested to represent subclinical markers of genetic susceptibility and indicators of genetic heterogeneity in ulcerative colitis (UC). However, results from more recent studies have contradicted this statement. To address this discrepancy, we assayed perinuclear neutrophil antibodies in the UC-affected members of 53 families with at least one relative pair affected with UC. METHODS: Perinuclear neutrophil antibodies were detected using an indirect immunofluorescence assay. RESULTS: Perinuclear neutrophil antibodies were present in 53% of the study subjects with ulcerative colitis (UC). In 15 families (28%), all members with UC were positive for perinuclear neutrophil antibodies, whereas in 12 families (23%), none of the UC-affected members were positive. In the remaining 26 families (49%), the results for the UC-affected relatives were discordant. Similar results were found when only sibling pairs were evaluated. Statistical analysis revealed that for all affected relative pairings, observed concordance did not significantly exceed expected concordance. Logistic regression analyses demonstrated that the degree of relationship was not enough to predict concordance for perinuclear neutrophil antibodies, and that these antibodies are not markers of genetic heterogeneity. CONCLUSIONS: Perinuclear neutrophil antibodies are not markers for genetic susceptibility or indicators of genetic heterogeneity in UC.

Adult↗
PubMed2007

Family system characteristics and psychological adjustment to cancer susceptibility genetic testing: a prospective study.

This study examined prospectively the contribution of family functioning, differentiation to parents, family communication and support from relatives to psychological distress in individuals undergoing genetic susceptibility testing for a known familial pathogenic BRCA1/2 or Hereditary nonpolyposis colorectal cancer-related mutation. Family functioning, differentiation to parents, hereditary cancer-related family communication and perceived support from relatives were assessed in 271 participants for genetic testing before test result disclosure. Hereditary cancer distress (assessed by the Impact of Event Scale) and cancer worry (assessed by the Cancer Worry Scale) were assessed before, 1 week after, and 6 months after test result disclosure. Participants reporting more cancer-related distress over the study period more frequently perceived the communication about hereditary cancer with relatives as inhibited, the nuclear family functioning as disengaged-rigid or enmeshed-chaotic, the support from partner as less than adequate and the relationship to mother as less differentiated. Especially, open communication regarding hereditary cancer and partner support may be important buffers against hereditary cancer distress. Identifying individuals with insufficient sources of support and addressing the family communication concerning hereditary cancer in genetic counseling may help the counselee to adjust better to genetic testing.

Adult↗
PubMed2002

Kininogen deficiency modulates chronic intestinal inflammation in genetically susceptible rats.

Genetically susceptible Lewis rats injected in the intestinal wall with peptidoglycan-polysaccharide (PG-APS) polymers develop chronic granulomatous enterocolitis concomitant with activation of the kallikrein-kinin system. To elucidate the role of high-molecular-weight kininogen (HK) in chronic enterocolitis, we back crossed Brown-Norway rats having a HK deficiency with Lewis rats for five generations. Two new strains were produced, wild-type F5 (F5WT) and HK deficient (F5HKd), each with a approximately 97% Lewis genome. The HK values of F5WT and F5HKd rat plasma were 0.62 +/- 0.20 and 0.08 +/- 0.03 U/ml, respectively. In PG-APS-injected rats, chronic inflammation was measured by using gross gut score, histological inflammation, liver granuloma, and white blood cell count. The mean gross gut scores were significantly lower in the F5HKd than in the F5WT rats. Plasma T-kininogen was significantly less in F5HKd. These results indicate the importance of the kallikrein-kinin system in this model of chronic enterocolitis and systemic inflammation.

Animals↗
PubMed2006

Review article: genetic susceptibility and application of genetic testing in clinical management of inflammatory bowel disease.

The volume of research undertaken on the genetic susceptibility of inflammatory bowel disease (IBD) has been tremendous, and over 10 chromosomal regions have been identified by genome-wide scanning. Fine-mapping approaches and candidate gene studies have already led to the identification of several susceptibility genes, including CARD15 (NOD2), DLG5, novel organic cation transporter (OCTN) 1 and 2, and CARD4 (NOD1). The CARD15 gene is the most understood at present and explains around 20% of the genetic predisposition to Crohn's disease. Although the clinical implications of genetic testing are limited at present, genetic research has advanced our understanding of the clinical heterogeneity and the complex interactions between genetic and environmental risk factors in IBD. Genes also interfere with the metabolism of drugs and may influence the clinical response and drug-related toxicity. Ultimately, researchers and clinicians aim to personalize medicine based on a patient's genotype, although azathioprine (thiopurine methyltransferase polymorphisms) is the only drug to date where pharmacogenetics has shown clinical relevance in IBD. In the future, it is anticipated that genetic markers will be implemented in an integrated molecular diagnostic and prognostic approach to managing our patients.

Colitis, Ulcerative↗
PubMed1998

A systematic study of oligodendrocyte growth factors as candidates for genetic susceptibility to MS. French Multiple Sclerosis Genetics Group.

OBJECTIVE: To test 23 genes coding for growth factors and their receptors as candidates for MS genetic susceptibility in 84 multiplex families of French origin by linkage analysis. BACKGROUND: Epidemiologic studies have indicated that genetic susceptibility in MS exists. To identify MS susceptibility genes, association and linkage studies were performed with candidate genes suggested by the pathology of MS. The most consistent result was genetic association and linkage of MS to human leukocyte antigen (HLA) DR15. Recent advances in the knowledge of MS pathology have suggested that the oligodendrocyte, the myelin-forming cell in the CNS, and its growth factors might play a crucial role in MS. METHODS: Fifty-two polymorphic markers within or flanking 23 candidate genes were used. Data were analyzed with the maximum likelihood score (MLS) approach. We also searched for a genetic interaction with HLA. RESULTS: Negative results were obtained for all candidate genes. The lower limits of the relative risk (Xs) possibly excluded for any candidate gene ranged from 1.3 to 2.8. Positive MLS values (up to 0.93) were observed for transforming growth factor beta 3 (TGFbeta3) in HLA DR15-associated families, suggesting a possible role for this growth factor in interaction with HLA. CONCLUSIONS: Oligodendrocyte growth factors do not play a significant role in MS genetic susceptibility, at least in the tested sample. TGFbeta3, the only gene highlighted by this study, deserves further analysis.

Adult↗
PubMed1991

Genetic susceptibility to Parkinson's disease.

Genetic factors clearly cause Lewy-body Parkinson's disease (PD) in a subset of autosomal-dominant families. However, most cases of PD are sporadic. The two most likely models of four discussed for sporadic PD are the reduced penetrance model and the multifactorial model. Sporadic PD is likely to be caused by the combined effect of environmental precipitating factors and genetic susceptibility factors. Because the number of major genetic factors is likely to be small, these hypotheses can be tested and genetic factors located using linkage mapping techniques. The affected pair analysis methods are especially suited to PD. Finding the genetic susceptibility factors for PD is important because this may be the fastest way to identify the environmental precipitating factors and because it may lead to prevention of PD. Because of the usefulness of identifying genetic susceptibility factors for PD, we are carrying out linkage studies in a group of 16 large autosomal-dominant families with PD and more than 300 living affected PD pairs.

Diseases in Twins↗
PubMed1991

Genetic susceptibility to Parkinson's disease.

Genetic factors clearly cause Lewy-body Parkinson's disease (PD) in a subset of autosomal-dominant families. However, most cases of PD are sporadic. The two most likely models of four discussed for sporadic PD are the reduced penetrance model and the multifactorial model. Sporadic PD is likely to be caused by the combined effect of environmental precipitating factors and genetic susceptibility factors. Because the number of major genetic factors is likely to be small, these hypotheses can be tested and genetic factors located using linkage mapping techniques. The affected pair analysis methods are especially suited to PD. Finding the genetic susceptibility factors for PD is important because this may be the fastest way to identify the environmental precipitating factors and because it may lead to prevention of PD. Because of the usefulness of identifying genetic susceptibility factors for PD, we are carrying out linkage studies in a group of 16 large autosomal-dominant families with PD and more than 300 living affected PD pairs.

Diseases in Twins↗
PubMed1978

Abortive poliomyelitis or minor illness as a clue to genetic susceptibility.

The model of genetic susceptibility to poliomyelitis has been used to examine minor illness caused by poliovirus infection. It is suggested that persons who are genetically susceptible but who have not converted to phenotypic susceptibility are those who develop minor illness. The overall rates of the sum of paralytic and minor illness are close to the predicted 26%. For families with a case of illness, the prediction that 58%--71% of the children become ill has been examined. The rates of illness in children of different ages in the same families should be similar. Data from a number of epidemics is shown to be consistent with the predictions of the model.

Adolescent↗
PubMed1997

Evidence for multiple genetic susceptibility loci for asthma.

Genetic susceptibility to asthma is due to multiple genes that interact with each other and the environment. There are many known environmental influences, such as viral and other respiratory infections and exposure to allergens, air pollutants, and active or passive cigarette smoke (1). Genome-wide screens for asthma and atopy have been completed and show statistical evidence for linkage in different racial groups and population samples (4, 5). Some of these linkages have already been replicated in different studies, and most of them are in chromosomal regions containing relevant candidate genes that may regulate inflammatory processes including cytokine synthesis, T-cell responses, or other immune functions. These associations support the relevance of this genetic approach in understanding susceptibility to and expression of asthmatic and allergic phenotypes. Once specific sequence variants are identified, it will become important to test for gene-environment interaction in order to understand the significance and relative effect of each gene on the overall phenotype.

Asthma↗
PubMed2000

Cytokines in genetic susceptibility to multiple sclerosis: a candidate gene approach. French Multiple Sclerosis Genetics Group.

The immune system is involved in the pathophysiology of multiple sclerosis (MS) but the initiating antigen(s) is not yet identified. Since cytokines control both the intensity and the quality of the immune response they may be relevant candidates for the genetic susceptibility to MS. To analyze the contribution of type 1 and type 2 cytokine and cytokine receptor genes in the genetic susceptibility to MS, we have examined, in 116 French MS sibpairs, whether there is significant linkage between MS and 15 cytokine or cytokine receptor genes using 31 highly polymorphic genetic markers. The data were analyzed using the maximum likelihood score and the transmission disequilibrium approaches. None of the candidate genes tested was significantly linked to MS on the whole population. However, after stratification of the analysis on the basis of sharing (or not) of the HLA-DRB1*1501 allele, indication of linkage was found for the IL2-RB gene. These findings suggest that the IL2-RB locus contributes to the genetic susceptibility in a subgroup of MS patients.

Cytokines↗
PubMed2005

ENPP1/PC-1 K121Q polymorphism and genetic susceptibility to type 2 diabetes.

Genetic susceptibility modulates the impact of obesity on risk for type 2 diabetes. The present study evaluates the role of ENPP1 K121Q polymorphism in prediction of type 2 diabetes in three populations that differ in susceptibility to diabetes and environmental exposure. The three cohorts included 679 nonmigrant South Asians living in Chennai, India (223 with type 2 diabetes); 1,083 migrant South Asians living in Dallas, Texas (121 with type 2 diabetes); and 858 nonmigrant Caucasians living in Dallas, Texas (141 with type 2 diabetes). Patients with type 2 diabetes were included in these cohorts if they had diabetes onset before the age of 60 years. The prevalence of subjects carrying the polymorphic ENPP1 121Q allele was 25% in the nondiabetic group and 34% in the diabetic group of South Asians living in Chennai (P = 0.01). The prevalence in the nondiabetic and diabetic groups were 33 and 45% (P = 0.01) for the South Asians living in Dallas and 26 and 39% (P = 0.003) for the Caucasians. Although further replication studies are necessary to test the validity of the described genotype-phenotype relationship, our study supports the hypothesis that ENPP1 121Q predicts genetic susceptibility to type 2 diabetes in both South Asians and Caucasians.

Adult↗
PubMed2001

Association of polymorphisms of the transforming growth factor-beta1 gene with genetic susceptibility to osteoporosis.

Osteoporosis exhibits a substantial genetic component. Although polymorphisms of a variety of genes have been associated with bone mineral density and genetic susceptibility to osteoporosis, the genes responsible for these traits have not been definitively identified. We have shown that a T869-->C polymorphism of the transforming growth factor-beta1 gene, which results in a Leu-->Pro substitution at amino acid 10, is associated with bone mineral density in Japanese adolescents and postmenopausal women, with genetic susceptibility to both osteoporosis and vertebral fracture, and with the outcome of treatment for osteoporosis with active vitamin D. We have also shown that a C-509-->T polymorphism in the promoter region of this gene is associated with both bone mineral density and the prevalence of osteoporosis in postmenopausal women. In addition, analysis of combined genotypes for both the C-509-->T and T869-->C polymorphisms revealed that bone mineral density decreases and the susceptibility to osteoporosis increases with the number of T alleles. Thus, combined genotyping of the C-509-->T and T869-->C polymorphisms may prove beneficial in the prevention of osteoporosis in postmenopausal Japanese women. I review here the association of transforming growth factor-beta1 gene polymorphisms with genetic susceptibility to osteoporosis, which has provided insight into the function of transforming growth factor-beta1 as well as into the role of genetic factors in the development of osteoporosis.

Adolescent↗
PubMed2001

[Association of polymorphisms of the transforming growth factor-beta 1 gene with genetic susceptibility to osteoporosis].

Osteoporosis exhibits a substantial genetic component. Although polymorphisms of a variety of genes have been associated with bone mineral density and genetic susceptibility to osteoporosis, the genes responsible for these traits have not been definitively identified. We have shown that a T869-->C polymorphism of the transforming growth factor-beta 1 gene, which results in a Leu-->Pro substitution at amino acid 10, is associated with bone mineral density in Japanese adolescents and postmenopausal women, with genetic susceptibility to both osteoporosis and vertebral fracture, and with the outcome of treatment for osteoporosis with active vitamin D. We have also shown that a C-509-->T polymorphism in the promoter region of this gene is associated with both bone mineral density and the prevalence of osteoporosis in postmenopausal women. In addition, analysis of combined genotypes for both the C-509-->T and T869-->C polymorphisms revealed that bone mineral density decreases and the susceptibility to osteoporosis increases with the number of T alleles. Thus, combined genotyping of the C-509-->T and T869-->C polymorphisms may prove beneficial in the prevention of osteoporosis in postmenopausal Japanese women. I here review the association of transforming growth factor-beta 1 gene polymorphisms with genetic susceptibility to osteoporosis, which has provided insight into the function of transforming growth factor-beta 1 as well as into the role of genetic factors in the development of osteoporosis.

Adolescent↗
PubMed1993

Specific and natural antibody production during Salmonella typhimurium infection in genetically susceptible and resistant mice.

Genetically susceptible (C57BL/6) and resistant (CBA) mice were infected with an avirulent strain of Salmonella typhimurium and studied over a 35-day period for the production of antibodies directed against bacterial antigens including lipopolysaccharide (LPS) (specific antibodies) and antibodies directed against self antigens [natural antibodies (NAb)]. Antibodies directed against LPS and self antigens were detected by enzyme immunoassay (EIA) and those directed against other bacterial antigens by immunoblotting. We found that serum natural antibody titres in C57BL/6 and CBA mice were similar and correlated with the bacterial load in the spleen and liver. In C57BL/6 mice, anti-LPS antibodies remained polyreactive and of the IgM isotype. In contrast, CBA mice, after an early increase in polyreactive IgM anti-LPS antibodies, mounted a specific anti-LPS IgG antibody response. The immunoblotting results demonstrated that the IgM polyreactive antibodies in the resistant and susceptible mice recognized bacterial antigens of different molecular weights and that CBA, but not C57BL/6 mice, were able to produce IgG antibodies recognizing bacterial components. Our results suggest that the synthesis of antibodies directed against bacterial antigens and natural antibodies follow, at least partially, distinct pathways, but they do not allow us to determine whether these two antibody populations are produced by the same or distinct B-cell subpopulations.

Animals↗