Replies to post #142272 on Biotech Values

[DewDiligence]

I like your explanation for the omission of ApoA-1 Milano better than the explanation I gave earlier in this thread.

[urche]

HDL genetics

Thanks, Genisi. Please help me understand our understanding of the genetics of HDL.

I am wondering if HDL subtypes are well enough understood to show the relative cardioprotective or risk profile of each type of particle. If so, do you think we are at a point where a study of the genetics of HDL subtypes, one's personal HDL fingerprint, so to speak, could be traced to one's genes?

If so, then it seems plausible to start designing treatment more specific than just trying to raise HDL, which may be a target too blunt and complicated to be clinically useful.

That's a lot of ifs.

Urche

[vinmantoo]

genisi,

<Two reasons I can think of for not using the Milano variant, first ApoA-1 Milano is a mutation (not a polymorphism) and its gene pool is limited to a very small population mostly in Italy (all sharing a common ancestor), while the rest of us have the wild-type. >

All SNPs are mutations. What you refer to as the wild-type is merely the most wide-spread version of that protein in the general population, also called the reference allele in SNP studies. Some SNPs have no effect on the function of the protein, some do have effects that function. The postulate is that the ApoA-1 Milano SNP has some beneficial effect compared to the reference allele. I agree with the second part that the small genetic diversity of the population carrying the ApoA-1 Milano SNP makes it difficult to determine if it is the likely reason why there is a lower MI risk.