The paper, titled "Antisense Inhibition of APOC3
in Patients with Hypertriglyceridemia" (Gaudet et al, N Engl J Med 2015: published online July 29), reported data from the Phase 2 study of volanesorsen, a double-blind, randomized, placebo-controlled 13-week study designed to assess the safety and activity of volanesorsen in patients as a monotherapy and as an add-on to fibrates.
One in 20 Amish people has a mutation that destroys a gene, APOC3
, involved in triglyceride metabolism, as compared with one in 150 Americans generally.
In support, a genome-wide association study in the inbred Old Order Amish identified heterozygosity for a null mutation (R19X) in APOC3
(apolipoprotein C-III) resulting in lower triglycerides and a decrease in coronary artery calcification as a marker for subclinical atherosclerosis (8), suggesting that lifelong deficiency of apolipoprotein C-III promoting triglyceride hydrolysis may have a cardioprotective effect.
Finally, in 190 affected sibling pairs from a cohort of Asian Indian families with a strong history of premature coronary artery disease, the Sac-1 single nucleotide polymorphism in the APOC3
gene and hypertension were contributory factors to this atherogenic trait; circulating apoA-I in participants (distinct from HDL-cholesterol) was highly significantly and positively correlated with serum apoB and triglycerides (28).
Modeling the influence of APOC3
, APOE, and TNFpolymorphisms on the risk of antiretroviral therapy-associated lipid disorders.
The gene, known as APOC3
, produces a protein, apoC-III, that normally inhibits the breakdown of triglycerides.
The gene, known as APOC3
, produces a protein that normally inhibits the breakdown of triglycerides.
Ordovas and coworkers have also found mutations on APOB and APOC3
The researchers' findings, together with other recent genetic discoveries - specifically, the identification of protective mutations in the APOC3
gene that lower triglyceride levels and the risk of heart attack - refocus attention on abnormal triglyceride metabolism as an important risk factor for heart attack at any age.
13 (G) APOC3
, APOA1 13q34 rs4773144 COL4A1, COL4A2 0.
Pollin said that those with this mutation of the APOC3
gene have higher levels of HDL-cholesterol, the so-called "good" cholesterol, and lower levels of LDL-cholesterol, the "bad" cholesterol.
CMHC's unparalleled faculty will present novel research and treatment approaches ranging from the role of inflammation in CVD to significant genetic discoveries, including PCSK9 inhibition and APOC3
polymorphisms, to the bionic pancreas and the impact of gut microbiota on obesity.