MAPPING A GENE INVOLVED IN REGULATING DIETARY-CHOLESTEROL ABSORPTION - THE SITOSTEROLEMIA LOCUS IS FOUND AT CHROMOSOME 2P21

The molecular mechanisms regulating the amount of dietary cholesterol retained in the body as well as the body's ability to selectively excl ude other dietary sterols are poorly understood. Studies of the rare a utosomal recessively inherited disease sitosterolemia (OMIM 210250) ma y shed some light on these processes. Patients suffering from this dis ease appear to hyperabsorb both cholesterol and plant sterols from the intestine. Additionally, there is failure of the liver's ability to p referentially and rapidly excrete these non-cholesterol sterols into b ile. Consequently, people who suffer from this disease have very eleva ted plasma plant sterol levels and develop tendon and tuberous xanthom as, accelerated atherosclerosis, and premature coronary artery disease . Identification of this gene defect may therefore throw light on regu lation of net dietary cholesterol absorption and lead to an advancemen t in the management of this important cardiovascular risk factor. By s tudying 10 well-characterized families with this disorder, we have loc alized the genetic defect to chromosome 2p21, between microsatellite m arkers D2S1788 and D2S1352 (maximum lodscore 4.49, theta = 0.0).