Susceptibility, genetic

Extensive research is currently underway to use biological markers (biomarkers) in exposure and risk assessment. Biomarkers include the reaction products of chemicals or their metabolic products with biological macromolecules, especially with DNA. They also involve indicators of effect, such as chromosomal damage, and indicators of individual genetic susceptibility. 

NF-xB activation has been linked with atherosclerosis (Andalibi etal., 1993 Liao etui., 1993). Mice that were maintained on an atherogenic diet, which resulted in ox-LDL accumulation in the liver and arteries, showed NF-xB activation in hepatic tissues. Furthermore, inflammatory gene up-regulation corresponded to the concentration of accumulated lipid peroxides as well as genetic susceptibility to fetty-streak development. 

The genetic basis for the more common late-onset AD appears more complex. Genetic susceptibility is more sporadic and it may be more dependent on environmental factors.9 The apolipoprotein E (apo E) gene on chromosome 19 has been identified as a strong risk factor for late-onset AD. There are three variants of apo E however, carriers of two or more of the apo E4 allele have an earlier onset of AD (approximately 6 years earlier) compared with non-carriers.9 Only 50% of AD patients have the apo E4 allele, thus indicating it is only a susceptibility marker. 

Besides age, the development of colorectal cancer appears to be caused by variety of dietary or environmental factors, comor-bid disease states, and genetic susceptibility to the disease. Table 88-1 lists well-known risk factors for developing colon cancer. Epidemiologic studies of worldwide incidence of colorectal... 

Mange KC, Prak EL, Kamoun M, et al. Duffy antigen receptor and genetic susceptibility of African Americans to acute rejection and delayed function. Kidney Int 2004 66 1187-1192. 

Yoshitomi H, Sakaguchi N, Kobayashi K, et al. A role for fungal fi-glucans and their receptor Dectin-1 in the induction of autoimmune arthritis in genetically susceptible mice. J Exp Med 2005 201(6) 949-960. 

Lee BN Department of Veterans Affairs, Medical Center, Sepulveda, CA Test effect of lead on blood pressure (Bp) in three different strains of rats with different genetic susceptibility to the development of hypertension Department of Veterans Affairs, Research and Development... 

Nelson LM Stanford University, Stanford, CA Investigate the role of environmental toxicants and genetic susceptibility factors in the etiology of ALS National Institute of Environmental Health Sciences... 

Swaroop, A, Branham, KEH, Chen, W, and Abecasis, G, 2007. Genetic susceptibility to age-related macular degeneration A paradigm for dissecting complex disease traits. Hum Mol Genet 16, R174—R182. 

Weatherall D, Clegg J, Kwiatkowski D. The role of genomics in studying genetic susceptibility to infectious disease. Genome Res 1997 7[10] 967-973. Bellamy R, Ruwende C, Corrah T, McAdam KP, Whittle HC, Hill AV. Variations in the N RAM PI gene and susceptibility to tuberculosis in West Africans. N Engl J Med 1998 338(10] 640—644. 

Hood HM, Buck KJ. Allelic variation in the GABA-A receptor yl subunit is associated with genetic susceptibility to ethanol-induced motor incoordination and hypothermia, conditioned taste aversion, and withdrawal in BxD/Ty recombinant inbred mice. Alcohol Clin Exp Res 2000 24 1327-1334. 

The answer is e. (Kat ung, pp 428-429J Although a rare occurrence, halothane and other inhaled gas anesthetics may cause malignant hyperthermia Apparently, this occurs in genetically susceptible individuals Its onset may be accelerated by the concomitant use of succinylcholine. Immediate treatment includes administration of dantrolene. 

However, no single genetic susceptibility factor for late-onset PD has yet received anything like the same degree of support as APOE-s4 in late-onset AD (see above). 

Acquired human prion diseases include kuru and variant CJD 794 Prion protein polymorphism contributes genetic susceptibility to prion disease 794... 

The concordance rate of mood disorders is 60-80% for monozygotic twins and 14-20% for dizygotic twins. Linkage studies suggest that certain loci on genes and the X chromosome may contribute to genetic susceptibility of bipolar disorder,... 

Tests with relatively low predictive values may be useful in a few situations. First, testing may be valuable when the ADR in those with a testable genetic susceptibility at standard therapeutic dosages occurs suddenly and becomes irreversible or life-threatening before the drug can be stopped. Testing before administration of the standard dose would prevent these ADRs but would... 

Although African Americans and whites share many of the same genetic susceptibilities, some racial differences in the incidence or significance of certain disease predictions may exist. In some cases, African Americans may have a risk that whites do not. For example, researchers have recently found that a mutation in the gene coding for a protein essential for blood clotting... 

Kleeberger, S.R., et al., Genetic susceptibility to ozone-induced lung hyperpermeability Role of toll-like receptor 4, Am. J. Respir. Cell. Mol. Biol. 22, 5, 620, 2000. 

Another species may not be genetically susceptible to the toxic effect. 

Is the effect reversible Reversibility of a response is dependent on the drug itself, exposure levels/duration, and factors related to the test animal (metabolic capability, genetic susceptibility, etc.). Most effects produced by immunosuppressive drugs have been shown to be reversible after cessation of therapy, such as those produced during cancer chemotherapy. However, if a tumor develops before the immune system is restored, the effect is not reversible, as is the case of secondary tumors related to chemotherapy. 

Motulsky A. Nutrition and genetic susceptibility to common diseases. Am J Clin Nutrition 1992 55 1244S1245S. 

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