Gain-of-function and loss-of-function PCSK9 mutations
| Gain-of-function mutations | |||
|---|---|---|---|
| PCSK9 variant | Population | Clinical characteristics | |
| D374Y | British, Norwegian, families;1 Utah family | Premature CVD, tendon xanthomas, severe hypercholes terolemia | |
| S127R | French, South African, Norwegian families | Tendon xanthomas, CVD, early MI, stroke | |
| R215H | Norwegian family | Brother died at 31 from MI; strong family history of CVD | |
| Loss-of-function mutations | |||
|---|---|---|---|
| PCSK9 variant | Population | LDL-C | CVD risk |
| R46L | ARIC, DHS | ↓ 15% | ↓ 47% |
| Y142X or C679X | ARIC, DHS | ↓ 28%–40% | ↓ 88% |
| R46L CGPS | ↓ 11% | ↓ 46% | |
ARIC = Atherosclerotic Risk in Communities study; CGPS = Copenhagen General Population Study; CVD = cardiovascular disease; DHS = Dallas Heart Study; MI = myocardial infarction
Data from references 25–29.