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At least 289 records · Page 16Linked to original sources
PubMed2005

Will genetic testing for complex diseases increase motivation to quit smoking? Anticipated reactions in a survey of smokers.

The aim of this study was to improve understanding of smokers' potential reactions to genetic testing for smoking-related diseases. One thousand twenty-four respondents completed a postal survey; 186 were smokers. Questions addressed anticipated psychological and behavioral reactions to genetic test results using hypothetical scenarios. Of smokers, 65% anticipated being motivated to quit smoking upon receiving a positive genetic test result; 39% anticipated being demotivated by a negative result. More smokers anticipated being depressed in response to receiving a positive result for cancer than for heart disease (40% vs. 24%). Anticipated motivation was associated with higher desire to quit and lower nicotine addiction, anticipated depression with poorer understanding of genetic testing, and anticipated demotivation with lower education. Smokers who have a high desire to quit may use genetic testing as a motivational tool. Understanding of genetics may be important in determining how individuals respond to genetic tests for complex diseases.

Adolescent↗
PubMed2000

Familial pulmonary Mycobacterium avium complex disease.

We report two Japanese families affected by pulmonary Mycobacterium avium complex (MAC) disease, involving an older brother and younger sister in one family and two brothers in the second family. We investigated whether defects in the natural resistance-associated macrophage protein gene (NRAMP1) underlay susceptibility to MAC in these cases. All of the patients had computed tomographic findings of peripheral nodules and bronchiectasis. Pulse-field gel electrophoresis patterns of mycobacterial genomic DNA restriction fragments revealed that none of the MAC strains isolated from the patients was epidemiologically related to any of the others. Direct sequencing of the complementary DNA of the patients' NRAMP1 revealed a nonconservative missense mutation at codon 419 in one patient, which was heterozygous and was not seen in his affected sibling. No variations similar to those found in mice that show susceptibility to MAC were found. The results suggest an underlying genetic defect in host defense rather than exposure to an unusually virulent strain of MAC as the pathogenetic factor in MAC disease; however, alterations in the coding region of NRAMP1 do not appear to explain the susceptibility to MAC.

Adult↗
PubMedDate not supplied

Experimental immune complex disease of the intestine.

The effect of immune complex deposition in intestine was studied in a mercuric chloride-induced experimental autoimmune disease model in the Brown Norway rat. Whereas deposition of autoantibodies in a linear pattern along the basement membrane did not lead to any functional changes, presence of immune complexes along the intestinal basement membrane, occurring after week 35 of the experiment, was associated with intestinal protein loss.

Animals↗
PubMed1997

Small genetic effects in complex diseases: a review of regulatory sequence variants in dyslipoproteinemia and atherosclerosis.

OBJECTIVE: Most reported mutations that affect lipoprotein metabolism are found within the coding sequences of genes. Recently, a few mutations that occur within promoter sequences have been detected. These promoter sequence variants are the topic of the present review. METHODS: Some of these variants are fairly common genomic variants in the promoter regions for candidate genes in lipoprotein metabolism, such as APOA1, APOC3, LPA, and LPL. It is possible that such regulatory sequence variants can result in chronic, modestly altered levels of expression of qualitatively normal gene products. This might have a cumulative effect on quantitative phenotypes, such as plasma lipoprotein concentrations, over the long term. Such an effect might not be detected by existing clinical, biochemical, and/or physiological assays. RESULTS: At present, the most consistent evidence from several lines of experiments indicates that genomic variation in the APOC3 promoter creates slightly elevated plasma triglyceride concentrations within the physiologic range. This altered expression appears to predispose to hypertriglyceridemia in the presence of secondary factors. Genetic variants that produce small effects on promoter function might thus be one component of the predisposition to complex diseases. CONCLUSION: The aggregate of many small effects may create or contribute to a background of susceptibility that, under appropriate conditions, leads to development of frank dyslipidemia and atherosclerosis.

Apolipoprotein A-I↗
PubMed1994

LABMAN and LINKMAN: a data management system specifically designed for genome searches of complex diseases.

Two programs have been developed to manage linkage analysis data. The first program, LABMAN, is a comprehensive laboratory data management system organizing pedigrees, blood DNA samples, DNA markers, Southern blot or polyacrylamide gels, autoradiographs, and marker-allele typings generated from these samples. Output includes mendelization checks for genetic incompatibilities in typings and formatted files ready for linkage analysis. LABMAN can also compress highly polymorphic allele systems into smaller allele systems facilitating analysis of large systems. The second program, LINKMAN, provides data management for lod score output from linkage analyses. It reads linkage analysis output files, calculates lod scores by family, associates lod scores with specific marker and family identifiers, and stores these data in a database where they can be combined with lod scores from previous analyses. LINKMAN easily incorporates any of a wide variety of genetic models. It produces formatted output of lod scores by user-specified criteria for reports or as ASCII files for input to other programs. If desired, tests of homogeneity of linkage across families can be run via the HOMOG program [Ott, 1991] and their output included in reports. The programs include features critical for conducting genome searches of complex diseases: They are easy-to-use, well-tested, and reliable. Data from multicenter investigations can be easily combined for analysis. Moreover, they include extensive error-checking capabilities, and they are specifically set up to protect blindness between laboratory workers and data analysts. LABMAN and LINKMAN are currently available free of charge under DOS.

Alleles↗
PubMed2006

Genomic DNA pooling for whole-genome association scans in complex disease: empirical demonstration of efficacy in rheumatoid arthritis.

A pragmatic approach that balances the benefit of a whole-genome association (WGA) experiment against the cost of individual genotyping is to use pooled genomic DNA samples. We aimed to determine the feasibility of this approach in a WGA scan in rheumatoid arthritis (RA) using the validated human leucocyte antigen (HLA) and PTPN22 associations as test loci. A total of 203 269 single-nucleotide polymorphisms (SNPs) on the Affymetrix 100K GeneChip and Illumina Infinium microarrays were examined. A new approach to the estimation of allele frequencies from Affymetrix hybridization intensities was developed involving weighting for quality signals from the probe quartets. SNPs were ranked by z-scores, combined from United Kingdom and New Zealand case-control cohorts. Within a 1.7 Mb HLA region, 33 of the 257 SNPs and at PTPN22, 21 of the 45 SNPs, were ranked within the top 100 associated SNPs genome wide. Within PTPN22, individual genotyping of SNP rs1343125 within MAGI3 confirmed association and provided some evidence for association independent of the PTPN22 620W variant (P=0.03). Our results emphasize the feasibility of using genomic DNA pooling for the detection of association with complex disease susceptibility alleles. The results also underscore the importance of the HLA and PTPN22 loci in RA aetiology.

Arthritis, Rheumatoid↗
PubMed2007

An investigation of the effects of endometriosis on the proteome of human eutopic endometrium: a heterogeneous tissue with a complex disease.

The pathogenesis of endometriosis includes the proliferation of heterogeneous endometrial cells and their invasion into ectopic sites within the peritoneal cavity. This may be due to abnormalities of the eutopic endometrium itself, predisposing the cells to survive and implant ectopically. We investigated the applicability of 2-DE gels and peptide mass mapping to identify candidate endometrial proteins with a role in endometriosis. Despite the heterogeneous nature of endometrium, our results show that combining the analysis of 2-DE gels and peptide mass mapping yields consistent data. We identified dysregulated proteins in women with endometriosis which included: (i) molecular chaperones including heat shock protein 90 and annexin A2, (ii) proteins involved in cellular redox state, such as peroxiredoxin 2, (iii) proteins involved in protein and DNA formation/breakdown, including ribonucleoside-diphosphate reductase, prohibitin and prolyl 4-hydroxylase, and (iv) secreted proteins, such as apolipoprotein A1. These proteins have functions which suggest that they could play a role in the pathogenesis of endometriosis. This study demonstrated that 2-DE gel analysis and mass spectroscopic protein identification are suitable for the identification of proteins with candidate associations with endometriosis. These techniques should be used on a larger scale to identify endometriosis-related proteins, thus improving the understanding of this complex disease.

Adult↗
PubMed2003

Involvement of gene-diet/drug interaction in DNA methylation and its contribution to complex diseases: from cancer to schizophrenia.

Most biological processes, including diseases, involve genetic and non-genetic factors. Also, the realization of a genetic potential may depend on environmental factors by directly affecting the expression of gene(s). Exactly how different environmental factors affect gene expression is not well understood. One of the mechanisms may involve DNA methylation and thereby gene expression. Diet, chemicals, and metals are known to affect DNA methylation and other epigenetic processes but are just beginning to be elucidated. For example, methylation of cytosine(s) in the promoter region could prevent the binding of transcription factors or create binding sites for complexes that deacetylate neighboring histones that in turn compact the chromatin, encouraging a gene to become silent. This article will discuss DNA methylation as an epigenetic mechanism of gene regulation and examine how factors like diet, chemicals, and metals may affect DNA methylation. The effect of alterations in DNA methylation may include aberrant expression of genes or genomes and chromosomal instability, which in turn may contribute to the etiology of complex multifactorial diseases. A similar mechanism is now recognized in a number of cancers. There is also indirect evidence to suggest that methylation could apply to a number of complex diseases, including schizophrenia.

DNA Methylation↗
PubMed2002

Chinese National Twin Registry as a resource for genetic epidemiologic studies of common and complex diseases in China.

Twins, due to their unique genetic and environmental relationships, have provided crucial insight in our understanding of genetic contributions to numerous etiologically complex disorders in developed countries. As the leading cause of death and adult disability, cardio- and cerebrovascular diseases are common in China, followed by cancer. Obesity and psychological disorders are increasing. The overall goal of this program is to develop a resource for genetic epidemiologic studies of these and other common and complex diseases in China. Our initial focus is to delineate the genetic and environmental determinants of vascular diseases in general, coronary artery disease (CAD) and stroke in particular. To date, we have over 4500 twin pairs registered and about 700 twin pairs studied for various metabolic traits (e.g., lipids, glucose, insulin, etc.). The long-term plan of this program is to (1) establish a population-based twin registry from several selected regions in China for future studies of specific common complex diseases; (2) conduct detailed phenotyping for clinical and intermediate traits related to cardiovascular diseases; (3) expand studies of twins to twin families by including their parents, siblings, and offspring for genetic linkage and association studies; and (4) follow up twins in the registry longitudinally. The goals of the program are health education and promotion of healthy behavior, early identification of cases to provide timely medical attention, and the evaluation of long-term effects of identified risk factors. We want to develop collaborations with investigators who have expertise in cancer, psychological disorders, and other disease areas.

Adolescent↗
PubMed1988

A new experimental model of in-situ immune complex disease of the lung.

A model of acute immunological lung injury, initiated by the binding of passively administered antibody to an antigen (Concanavalin A (Con A] affixed to the pulmonary endothelium, is described. Pulmonary injury, monitored using the 125I-albumin lung permeability index (LPI) did not occur with antigen deposition alone (LPI 0.235 +/- 0.012). The binding of antibody to the 'planted' lung antigen resulted in injury only when antibody binding exceeded a threshold value of 7.4 +/- 1.4 micrograms antibody globulin per gram of lung. Alevolar-capillary permeability changes were maximal 4 to 8 h after antigen-antibody interaction (LPI at 2 h, 0.353 +/- 0.015: at 4 h, 0.387 +0.33; at 8 h, 0.373 +/- 0.025; at 24 h, 0.289 +/- 0.031; at 48 h, 0.239 +/- 0.022). Lung injury was significantly attenuated by neutrophil (PMN) depletion (LPI at 4 h, 0.325 +/- 0.014: P less than 0.01cf PMN-intact animals), and further reduced by complement depletion (LPI at 4 h, 0.275 +/- 0.023: P less than 0.05 cf PMN-intact and PMN-deplete animals). This model of immune lung injury demonstrates the potential for in situ immune reactions on the pulmonary endothelial surface to induce acute inflammatory injury. Further the model illustrates the cooperative effects of neutrophils and complement in the genesis of inflammation, with both these mediator systems contributing to immunological pulmonary injury.

Acute Disease↗
PubMed1989

The genetics of Crohn disease: complex segregation analysis of a family study with 265 patients with Crohn disease and 5,387 relatives.

We have analysed the pedigrees of 265 probands with Crohn disease, collected from a specialty clinic at the University of Düsseldorf. Complex segregation analysis suggests the presence of a recessive gene with incomplete penetrance for susceptibility to the disease with no residual causes of family resemblance. However, a proportion of the isolated cases are probably due to phenocopies, this proportion being greatest among cases with an advanced age of onset.

Chromosome Mapping↗