Polymorphisms disease, risk factors

Voutilainen, S. et al.. Functional COMT Vall58Met polymorphism, risk of acute coronary events and serum homocysteine The Kuopio Ischaemic Heart Disease Risk Factor Study, PloS ONE, 2 (1), el81, 2007. 

The second area of growing importance is that of susceptibility to disease. It has long been known that some common diseases run in families, although it was not known why. For the same reason, known disease risk factors carry very different levels of risk for different individuals. For example, in Topic 19 we met LDL, one of the proteins associated with transport of cholesterol. This has to dock with a specific protein receptor, the LDL receptor, at cell surfaces. A variety of mutations in the gene for the LDL receptor cause familial hypercholesterolaemia affected individuals have a much enhanced risk of heart disease. Detailed study of the human genome is likely to throw up many more correlations of this kind for various kinds of cancer and other diseases. It has recently been found that a polymorphism related to survival of mediaeval plague epidemics may also be responsible for certain individuals remarkable resistance to the HIV infection that causes AIDS ... 

Lanthanides are particularly well-suited for multilabel assays due to their narrow line type emissions and varying decay times. Combination of different lanthanide donors where each of them may apply a set of different acceptors and create ET signal at different wavelength and decay times is also applied in bioanalytical assays, particularly in DNA hybridization assays in measuring single nucleotide polymorphic (SNP) alleles related to disease risk factors. 

Moatti D, Faure S, Fumeron F, et al. Polymorphism in the fractalkine receptor CX3CR1 as a genetic risk factor for coronary artery disease. Blood 2001 97(7) 1925-1928. 

Ghilardi G, Biondi ML, Turri O, Guagnellini E, Scorza R. Internal carotid artery occlusive disease and polymorphisms of fractalkine receptor CX3CR1 a genetic risk factor. Stroke 2004 35(6) 1276-1279. 

In addition, haplotype-based methods can increase the power of association studies since the allelic architecture of the risk factor is unknown. Recent examples of association studies suggest that haplotypes can be the responsible factors [58]. The Apo E4 allele , which is associated with Alzheimer s disease, is a possible example since it results from the substitution of two of non-conservative polymorphisms encoding for residues 112 and 158 [59]. 

Lipoprotein (a) is an independent risk factor for coronary artery disease [68]. It consists of two components an LDL particle and apolipoprotein (a) which are linked by a disulfide bridge. Apo(a) reveals a genetically determined size polymorphism, resulting from a variable number of plasminogen kringle IV-type repeats [69]. Statins either do not affect Lp(a) or may even increase Lp(a) [70, 71]. In a study of 51 FH patients, treated with 40 mgd 1 pravastatin, it has been shown that the increase in Lp(a) was greatest in patients with the low molecular-weight apo(a) phenotypes [70]. 

A polymorphism can be a risk factor for an individual s health or life expectancy without impairing its reproduction. This appears to be the case for many common human diseases, which manifest themselves only after the generative period, so that evolutionary selection against such a trait cannot be operative. 

Borroni, B., Archetti, S., Agosti, C., et al. (2004) Intronic CYP46 polymorphism along with APOE genotype in sporadic Alzheimer s disease from risk factors to disease modulators. Neurobiol. Aging, 25, 747-751. 

Wang GQ, DiPietro M, Roeder K et al. Cladistic analysis of human apolipoprotein a4 polymorphisms in relation to quantitative plasma lipid risk factors of coronary heart disease. Ann Hum Genet. 2003, 67 107-124. 

Many studies published during the last few decades have suggested that hyperhomocysteinemia is a risk factor for coronary artery disease (CAD), stroke, and thromboembolic disease. The Homocysteine Studies Collaboration metaanalysis of 30 studies concluded that elevated tHcy is a moderate risk factor for ischemic heart disease a level 3 xmol/L lower reduces the risk with an odds ratio of 0.89 (95% Cl = 0.83-0.96). The same was true for homocysteine as a risk factor for stroke (odds ratio = 0.81 95%5CI = 0.69-0.95) (6). A meta-analysis of 40 studies of the MTHFR 677 C > T polymorphism demonstrated a mildly increased risk of coronary heart disease with an odds ratio of 1. 16 (95% Cl = 1.05-1.28) (25). 

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