Hypercholesterolemia polymorphism

In addition to the frequency considerations attendant to the examination of polymorphisms or haplotypes, one must also consider the impact of possible differences in the magnitude of effects of any putative loci. The magnitude of any effects is denoted as "scale" effects based on the notion from quantitative genetics that there will be a displacement from the overall population mean for a trait that is dependent on genotype. To illustrate the effects of scale and frequency, consider two well-known examples of genetic effects. These are the effect of the apolipoprotein E (apo E) polymorphism on cholesterol levels and the impact of the familial hypercholesterolemia polymorphism on cholesterol levels. 

Mutations within the SREBPs and the SREBP processing proteins (SCAP, SIP, S2P) have intensively been searched, especially in patients with familial hypercholesterolemia. So far, however, only four polymorphic sites within SCAP [38, 39], one within the promoter of SREBP-la [40], and five mutations in SREBP-2 [41] have been published. Yet, the impact of these polymorphisms and mutations on the response to statins has not been evaluated. 

Without going into all the technical considerations, let s see how the allele conferring a particular dominant trait (e.g., familial hypercholesterolemia) might be mapped. The first step is to obtain DNA samples from all the members of a family containing individuals that exhibit the disease. The DNA from each affected and unaffected individual then is analyzed to determine the identity of a large number of known DNA polymorphisms (either SSR or SNP markers can be used). The segregation pattern of each DNA polymorphism within the family is then compared with the segregation of the... 

Although extrapolation to humans has not been reported, P450 7B1 is considered to be a neurosteroid hydroxylase and have a potentially important role . Functional polymorphisms in the human CYP7BI gene have not been reported, but have been postulated to lead to severe hypercholesterolemia and neonatal liver disease . 

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