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Results for “Genetic predisposition”

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At least 217 records · Page 12Linked to original sources
PubMed2004

Genetic predisposition to salt-sensitivity: a systematic review.

PURPOSE: To assess the role of genetic polymorphisms in salt sensitivity of blood pressure. DATA IDENTIFICATION: We conducted a systematic review by searching the Medline literature from March 1993 to June 2003. Each paper was scrutinized and data concerning study population, method of salt sensitivity testing, blood pressure measurement, definition of salt sensitivity, and effects were extracted. STUDY SELECTION AND DATA EXTRACTION: A total of 23 studies met the inclusion criteria. There was considerable heterogeneity in the method of salt sensitivity testing among the studies. Due to these differences, it was impossible to perform pooled analyses by genetic variants. Detailed investigation was done on the alpha-adducin Gly460Trp, ACE I/D, angiotensinogen M235T, G protein beta 3 C825T, aldosterone synthase gene and 11 beta-hydroxysteroid dehydrogenase type 2 G534A polymorphism. RESULTS AND CONCLUSIONS: Our analysis shows that the 460Trp variant of the alpha-adducin polymorphism is probably associated with a sodium-sensitive form of hypertension, while the polymorphisms of the angiotensin II type 1 receptor gene and the -344C/T variant of the aldosterone synthase gene are not associated with this phenotype. In view of the lack of standardization in salt sensitivity testing, we propose uniformity in study design in these type of studies.

Genetic Predisposition to Disease↗
PubMed2003

Genetic predisposition to infectious pathogens: a review of less familiar variants.

The susceptibility and clinical manifestations of infectious diseases in human populations are influenced by a variety of factors, among them host genetics. Obvious examples for the effect of host genetics on predisposition to unique infections are the primary immunodeficiency diseases. Minor gene variants that influence the host immune system are much more common. The iceberg model can be used to illustrate the epidemiology of immunodeficiency states. Accordingly only a few individuals have known and severe recognized primary immunodeficiencies, whereas many more patients have mild immunodeficiencies that may remain undiagnosed and are predisposed to a unique infectious disease. We review some of the less common variants that influence the host defense and predispose to certain infectious agents or change their outcome.

Animals↗
PubMed2005

Dual contribution of NR2B subunit of NMDA receptor and SK3 Ca(2+)-activated K+ channel to genetic predisposition to anorexia nervosa.

Since identification of the genetic component in anorexia nervosa (AN), genes that partake in serotonergic and dopaminergic systems and in hormonal and weight regulation have been suggested as potential candidates for AN susceptibility. We propose another set of candidate genes. Those are genes that are involved in the signaling pathway using NMDA-R and SK channels and have been suggested as possible effectors of NMDA-R driven signaling. The role of NMDA-R in the etiology of schizophrenia has already been substantiated on various levels. Several studies based on population and family groups have implicated SK3 in schizophrenia and more recently in AN as well. Our study group consisted of 90 AN family trios. We examined the transmission of two potentially functional polymorphisms, 5073T>G polymorphism in the gene encoding the NR2B subunit of NMDA-R and CAG repeats in the coding region of SK3 channel gene. Using HHRR and TDT approaches, we found that both polymorphisms were preferentially transmitted to AN offspring (TDT yielded chi(2)=5.01, p=0.025 for NR2B 5073G alleles and chi(2)=11.75, p<0.001 for SK3 L alleles including >19 repeats). Distribution analysis of the combined NR2B/SK3 genotypes suggests that the contribution of both polymorphisms to AN risk is independent and cumulative (OR=2.44 for NR2B GG genotype and OR=3.01 for SK3 SL and LL genotypes, and OR=6.8 for the combined NR2B/SK3 genotypes including high-risk alleles). These findings point to the contribution of genes associated with the NMDA-R signaling pathway to predisposition and development of AN.

Adolescent↗
PubMedDate not supplied

Genetic predisposition of cholesterol gallstone disease.

Gallstone disease (GSD) is the result of the interaction between genetic and environmental factors and it is a major disease cause of surgery with high costs to health systems. Worldwide prevalence varies according to the ethnic population suggesting that high prevalence of GSD in certain ethnic groups is due to the presence of genetic factors implicated in different metabolic pathways. However, environmental factors play a determinant role in gene expression. This review summarizes the genes involved in biliary salt and cholesterol synthesis, lipids transport and the Lith genes. Future studies should be focused on the study of interactions between genetic and environmental factors which could be specific for each population.

Animals↗
PubMedDate not supplied

Genetic predisposition to 4NQO-induced tongue carcinogenesis in the rat.

OBJECTIVE: This study aims to elucidate the genetic basis of predisposition to 4-nitroquinoline 1-oxide (4NQO)-induced tongue cancers (TCs). MATERIALS AND METHODS: We have reported that inbred Dark-Agouti (DA) strain rats were highly susceptible to 4NQO-induced TCs, whereas Wistar/Furth (WF) rats were resistant to tongue squamous cell carcinomas induced by oral administration of 4NQO. Using size and number of the tumours as quantitative parameters, responsible host loci were analysed by an interval mapping of F2 intercross of DA and WF given carcinogenic regimen. Also, loss of heterozygosity (LOH) at these loci was analysed in tongue cancers in (DA x WF) F1. RESULTS: We identified and mapped 5 significant quantitative trait loci (QTL), the Tongue squamous cell carcinoma 1-5 (Tscc1-5), and several other suggestive QTL that determine susceptibility to 4NQO-induced TC. Study of TCs induced in (DA x WF)F1 rats revealed a high frequency of LOH in the chromosomal regions of Tscc2, 3, and 4 and also of suggestive QTL on chromosomes 5 and 6. The fact that LOH was found only in larger TCs indicates that LOH occurred in the process of tumour progression. In most LOH, the allele of the resistant WF strain was lost, suggesting that these loci may encode tumour suppressor genes. In larger TCs, in addition to LOH, point mutations and the methylation of possible candidate genes were accumulated. CONCLUSION: These observations indicate that the 4NQO-induced TC in the rat is a multifactorial disease of a polygenic trait. This model will be useful to understand the complicated genetic basis of predisposition to oral cancers.

4-Nitroquinoline-1-oxide↗
PubMed2004

Efficacy of MRI and mammography for breast-cancer screening in women with a familial or genetic predisposition.

BACKGROUND: The value of regular surveillance for breast cancer in women with a genetic or familial predisposition to breast cancer is currently unproven. We compared the efficacy of magnetic resonance imaging (MRI) with that of mammography for screening in this group of high-risk women. METHODS: Women who had a cumulative lifetime risk of breast cancer of 15 percent or more were screened every six months with a clinical breast examination and once a year by mammography and MRI, with independent readings. The characteristics of the cancers that were detected were compared with the characteristics of those in two different age-matched control groups. RESULTS: We screened 1909 eligible women, including 358 carriers of germ-line mutations. Within a median follow-up period of 2.9 years, 51 tumors (44 invasive cancers, 6 ductal carcinomas in situ, and 1 lymphoma) and 1 lobular carcinoma in situ were detected. The sensitivity of clinical breast examination, mammography, and MRI for detecting invasive breast cancer was 17.9 percent, 33.3 percent, and 79.5 percent, respectively, and the specificity was 98.1 percent, 95.0 percent, and 89.8 percent, respectively. The overall discriminating capacity of MRI was significantly better than that of mammography (P<0.05). The proportion of invasive tumors that were 10 mm or less in diameter was significantly greater in our surveillance group (43.2 percent) than in either control group (14.0 percent [P<0.001] and 12.5 percent [P=0.04], respectively). The combined incidence of positive axillary nodes and micrometastases in invasive cancers in our study was 21.4 percent, as compared with 52.4 percent (P<0.001) and 56.4 percent (P=0.001) in the two control groups. CONCLUSIONS: MRI appears to be more sensitive than mammography in detecting tumors in women with an inherited susceptibility to breast cancer.

Adult↗
PubMed2001

[Genetic predisposition to development of toxic liver cirrhosis caused by alcohol].

Comprehensive analysis of the contribution of genetic factors into predisposition to alcoholic toxic cirrhosis (TC) was performed. The ABO, RH, HP, TF, GC, PI, ACP1, PGM1, ESD, GLO1, and GST1 genetic polymorphisms were compared in 34- to 59-year-old male TC patients and control donors of the same sex and age. The phenotypic frequencies in the TC group deviated from the theoretically expected values; the main difference was the excess of rare homozygotes for the loci GC, ACP1, ESD, and GLO1. In the TC patients, the observed heterozygosity (Ho) was considerably lower than the theoretically expected value (H(e)). Wright's fixation index (F) in the TC patients was 30 times higher than in the control group (0.0888 and 0.0027, respectively). The frequencies of PI*Z and PI*S, the PI alleles that are responsible for lower concentrations of proteinase inhibitor, were 12 and 6 times higher in the TC than in the control group. The TC patients exhibited a significantly higher frequency of the liver glutathione-S-transferase GST1*0 allele, whereas the GST1*2 frequency was two times higher in the control subjects than in the TC patients (0.2522 and 0.0953, respectively). The TC and control groups showed statistically significant differences in the frequencies of the following alleles of six independent loci: ABO*0, TF*C1, TF*C2, PI*M1, PI*Z, ACP1*C, PGM1*1+, PGM1*1-, PGM1*2-, GST1*0, and GST1*2. The haptoglobin level was significantly higher and the serum transferrin level was drastically lower in all phenotypic groups of TC patients than in control subjects. The concentrations of IgM and IgG depended on the HP, GC, and PI phenotypes. The total and direct reacting bilirubin concentrations depended on the erythrocytic-enzyme phenotypes (ACP1, PGM1, and GLO1) in both TC and control groups.

Adult↗
PubMed1992

Can autoimmune mechanisms account for the genetic predisposition to schizophrenia?

Applications of molecular genetic techniques to schizophrenia have shown great initial promise but have then proved disappointing. In order to maximise chances of elucidating the genetic mechanism underlying schizophrenia, diverse strategies and diverse perspectives must be adopted. Most studies begin with the premise that, although schizophrenia may be a heterogeneous collection of diseases, some subtypes will be primarily single-gene disorders. We are concerned that this single-gene hypothesis may be incorrect. Schizophrenia research may benefit from application of knowledge from other disciplines and from other diseases which, in terms of epidemiology and apparent genetic mechanisms, bear some resemblance to schizophrenia.

Autoantibodies↗
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↗
PubMed2006

Genetic predisposition and health effect of occupational exposure to asbestos.

OBJECTIVES: As asbestos presents a direct genetic hazard for humans, a small-scale molecular epidemiological study was conducted to monitor 61 subjects long-term exposed to asbestos in comparison with 49 town controls and 21 control subjects from administration of the same factory. RESULTS: Asbestos exposed workers had significantly higher numbers of chromosomal aberrations compared with both control groups (P=0.003). Clinical examination showed that 44.3% of exposed workers developed symptoms of asbestosis. We were interested in the relationship between the risk of asbestos-coupled diseases and individual variability in biotransformation enzymes, especially in glutathione S-transferases and microsomal epoxide hydrolase. GSTP1*105Val allele appeared less in the group of workers with asbestosis compared to those without asbestosis (18.5% vs 34.7%, P=0.044), and in subjects with developed asbestosis coupled with bronchitis compared to those without bronchitis (0% vs 25%, P=0.048). Similarly, the genotype corresponding to low activity of microsomal epoxide hydrolase was significantly decreased in workers with fibrotic plaques compared to those without plaques (26.7% vs 56.3%, P=0.045). CONCLUSIONS: Our results suggest that GSTP1*105Val allele and low EPHX1 activity genotype may be protective for people occupationally exposed to asbestos. However, more extensive studies are needed to confirm our results.

Asbestos↗
PubMed2001

[Genetic predisposition to arterial and venous thrombosis].

Thrombosis is a multifactorial pathology. In addition to the environmental factors, there are genetic components which either predispose or protect against its occurrence. Some are common to only a small number of subjects: these are the high risk families to thrombotic disease. Others are present in a larger percentage of the general population: this is called polymorphism and its clinical expression is usually modest. The role of these genetic factors in the development of thrombosis is not easy to demonstrate, especially as there are many gene-gene and gene-environment interactions. Nevertheless, the genetic basis of venous thrombosis is well established and the value of this knowledge in the management of these patients is becoming recognised. On the other hand, there are many genetic factors in arterial pathology and the role of each taken in isolation is small. Well-targeted large scale trials are required to determine their effects.

Anticoagulants↗
PubMed2004

Genetic predisposition to heart failure.

This review describes the numerous and complex molecular systems that are either known players or candidates in heart failure(HF). All systems whose genetic background has been investigated to date in HF are listed and discussed. Discussion also includes functional notes and known genetic polymorphisms already investigated in HF or candidates that have not yet been investigated. Despite substantial research on HF, relatively few coordinated studies have been conducted that assign precise risk to specific genetic polymorphisms. Identification of risk associated with genetic variations and subsequent translation of genetic knowledge into clinical practice will likely progress only in cases of large coordinated studies based on identical standards. The potential result will be a more accurate definition of HF identified as an evolving complex of cardiovascular diseases.

Adenosine Monophosphate↗