lipoprotein metabolism - genetics

Question 1

lipoprotein particle responsible for cholesterol-CAD association

Answer 1

LDL

Question 2

lipoprotein particle responsible for TG-CAD association

Answer 2

remnants from VLDL or chylomicron

Question 3

lipid levels are __% genetic, __% non-genetic

Answer 3

60% genetic
40% non-genetic

Question 4

FH (familial hypercholesterolemia)

-aka
-symptoms
-abnormal lipids
-abnormal lipoproteins
-inheritance pattern
-mutations

Answer 4

(type IIa hyperlipoproteinemia)

atherosclerosis, early MI, xanthoma, lipid deposits in skin

hypercholesterolemia
elevated LDL

monogenic, autosomal co-dominant

LOF in LDLR, APOB
GOF in PCSK9

Question 5

familial chylomicronemia

-aka
-symptoms
-abnormal lipids
-abnormal lipoproteins
-inheritance pattern
-mutations

Answer 5

(type I hyperlipoproteinemia)

pancreatitis, eruptive xanthomas

hypertriglyceridemia
chylomicronemia

monogenic, autosomal recessive
LOF in LPL, APOC2

Question 6

familial dysbetalipoproteinemia

-aka
-symptoms
-abnormal lipids
-abnormal lipoproteins
-inheritance patterns
-mutations

Answer 6

(type III hyperlipoproteinemia)

early heart disease, xanthomas, pancreatitis

hyperTG & hyperchol
elevated IDL / CMR

autosomal recessive (90%)
LOF in APOE E2

autosomal dominant (10%)
LOF in APOE

Question 7

FHBL (familial hypobetalipoproteinemia)

-symptoms
-abnormal lipids
-abnormal lipoproteins
-inheritance pattern
-mutations

Answer 7

fatty liver, steatorrhea, cirrhosis

low TG, cholesterol
low VLDL / CM

monogenic, autosomal dominant
truncating in APOB
LOF in PCSK9

Question 8

ABL (abetalipoproteinemia)

-symptoms
-abnormal lipids
-abnormal lipoproteins
-inheritance pattern
-mutations

Answer 8

fatty liver, steatorrhea, neurological disorders, night blindness

low TG, cholesterol
absent VLDL / CM

monogenic, autosomal recessive
LOF in MTTP

Question 9

familial HDL deficiency

-aka
-symptoms
-abnormal lipids
-abnormal lipoproteins
-inheritance pattern
-mutations

Answer 9

(Tangier disease)

enlarged orange tonsils

lipids normal
low / absent HDL

monogenic, autosomal recessive
LOF in ABCA1 [impaired reverse cholesterol transport]

Question 10

statin drugs mechanism of action for lowering cholesterol

Answer 10

inhibits HMGCR (rate-limiting enzyme for cholesterol synthesis)

decreases LDL

Question 11

PCSK9 inhibitor drugs mechanism of action for lowering cholesterol

Answer 11

inhibits PCSK9
->
more LDLR on cell surface
->
more LDL uptake (so less LDL in blood)