Patel S B, Salen G, Hidaka H, Kwiterovich P O, Stalenhoef A F, Miettinen T A, Grundy S M, Lee M H, Rubenstein J S, Polymeropoulos M H, Brownstein M J
Center for Human Nutrition, University of Texas Southwestern Medical Center, Dallas, Texas 75235-9052, USA.
J Clin Invest. 1998 Sep 1;102(5):1041-4. doi: 10.1172/JCI3963.
The molecular mechanisms regulating the amount of dietary cholesterol retained in the body as well as the body's ability to selectively exclude other dietary sterols are poorly understood. Studies of the rare autosomal recessively inherited disease sitosterolemia (OMIM 210250) may shed some light on these processes. Patients suffering from this disease appear to hyperabsorb both cholesterol and plant sterols from the intestine. Additionally, there is failure of the liver's ability to preferentially and rapidly excrete these non-cholesterol sterols into bile. Consequently, people who suffer from this disease have very elevated plasma plant sterol levels and develop tendon and tuberous xanthomas, accelerated atherosclerosis, and premature coronary artery disease. Identification of this gene defect may therefore throw light on regulation of net dietary cholesterol absorption and lead to an advancement in the management of this important cardiovascular risk factor. By studying 10 well-characterized families with this disorder, we have localized the genetic defect to chromosome 2p21, between microsatellite markers D2S1788 and D2S1352 (maximum lodscore 4.49, theta = 0.0).
目前对于调节体内膳食胆固醇留存量以及机体选择性排除其他膳食固醇能力的分子机制了解甚少。对罕见的常染色体隐性遗传病谷甾醇血症（OMIM 210250）的研究或许能为这些过程提供一些线索。患有这种疾病的患者似乎会从肠道过度吸收胆固醇和植物固醇。此外，肝脏优先且快速地将这些非胆固醇固醇排泄到胆汁中的能力也出现障碍。因此，患有这种疾病的人血浆植物固醇水平会大幅升高，并会出现肌腱和结节性黄瘤、动脉粥样硬化加速以及早发性冠状动脉疾病。因此，鉴定该基因缺陷可能会有助于了解膳食胆固醇净吸收的调节机制，并推动对这一重要心血管危险因素的管理取得进展。通过对10个患有这种疾病的典型家族进行研究，我们已将该基因缺陷定位到2号染色体的2p21区域，位于微卫星标记D2S1788和D2S1352之间（最大对数优势分数为4.49，θ = 0.0）。
