Apo-AI (Apo-A1) Milano
Last reviewed 04/2021
- point mutations in apolipoproteinA1, the principal protein component of HDL, are associated with a wide variety of clinical phenotypes including amyloidosis
- cysteinearginine mutation at position 173 in the -helices of apoA-1 defines
the Apo Milano genotype:
- the Apo Milano genotype is associated with a reduction
in HDL levels but paradoxically is protective against atherosclerosis in man and
animal models
- the decrease in apoA-I levels among individuals with these structural mutations is the result of rapid catabolism of apoA-I (1)
- apoA-I Milano (2) results in an average 40% decrease in apoA-I and a 67% decrease in HDL-C (3)
- the Apo Milano genotype is associated with a reduction
in HDL levels but paradoxically is protective against atherosclerosis in man and
animal models
Reference:
- Franceschini G, Sirtori CR, Capurso A, Weisgraber KH, Mahley RW. A-IMilano apoprotein: decreased high-density lipoprotein cholesterol levels with significant lipoprotein modifications and without clinical atherosclerosis in an Italian family. J Clin Invest. 1980;66:892-900.
- Nichols WC, Dwulet FE, Liepnieks J, et al. Variant apolipoprotein AI as a major constituent of a human hereditary amyloid. Biochem Biophys Res Commun. 1988;156:762-768.
- Soutar AK, Hawkins PN, Vigushin DM, et al. Apolipoprotein AI mutation Arg-60 causes autosomal dominant amyloidosis. Proc Natl Acad Sci U S A. 1992;89:7389-7393.