Rare mutations may protect against heart disease

People with variations in key gene have reduced levels of bad cholesterol

Genetic mutations that inhibit production of a protein involved in cholesterol absorption show up in about 1 in 650 people, a study finds. These lucky few have lower levels of LDL, also known as the bad cholesterol, and substantial protection against heart disease, scientists report November 12 in the New England Journal of Medicine.

The protein, called Niemann-Pick C1-Like 1, facilitates movement of cholesterol from the small intestine into the bloodstream. People with one of the newly discovered mutations in the gene encoding this protein have lower levels of low-density lipoprotein. LDL delivers cholesterol to cells in the body, but excess LDL can contribute to plaque formation in coronary arteries, the hallmark of heart disease.

Scientists at Washington University in St. Louis and colleagues looked for mutations in the Niemann-Pick gene in more than 113,000 people, some with heart disease and some without. The search turned up 82 people carrying one of 15 mutations that switched off the gene’s protein production. These people carried only one functional copy of the gene instead of the usual two and their likelihood of heart disease was roughly halved. The carriers’ LDL cholesterol levels also averaged 12 points lower than non-carriers’ levels, but their scores for triglycerides and HDL, the good cholesterol, were similar.

A drug called ezetimibe, marketed as Zetia, lowers LDL by inhibiting the activity of the same Niemann-Pick protein. 

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