Brotherhood of genetics and preventive medication.

Staying in good health requires balance and harmony. This seems to apply specifically to the Niemann–Pick C1 Like 1 (NPC1L1) protein. If the transporter’s activity loses balance, i.e. absorbing either too little or too much cholesterol in the liver and intestine, the cholesterol concentration goes up either in bile or in serum. In the long run this may translate into either one of two evils: gallstones or a heart attack. This conclusion is brought aboutbya study presentedby Lauridsen et al. in this issue. The authors used a Mendelian randomization approach for studying the chromosomal locus of NPC1L1 and its inter-relationship with serum cholesterol and complex phenotypes. The transporter facilitates hepatic and intestinal cholesterol absorption. A higher activity removes more cholesterol from bile but increases its concentration in serum. Not surprisingly, the authors observed that presumably more active variants of NPC1L1 occur with higher serum cholesterol levels. The same variants increased the odds for vascular disease but had opposite effects on hospitalizations for gallstone disease. The apparent explanation for this quandary seems to be obvious. NPC1L1 contributes to the fate of cholesterol. Atherosclerosis is promoted when too much is reabsorbed into the serum. Vice versa, cholelithiasis occurs when bile is left with too much cholesterol and not enough bile salts.