Mapping a gene involved in regulating dietary cholesterol absorption - The sitosterolemia locus is found at chromosome 2p21
Mapping a gene involved in regulating dietary cholesterol absorption - The sitosterolemia locus is found at chromosome 2p21
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DOI：
10.1172/jci3963
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发表时间：
1998-09-01
影响因子：
15.9
通讯作者：
Brownstein, MJ
中科院分区：
文献类型：
--
作者：
Patel, SB;Salen, G;Brownstein, MJ
调节体内保留的膳食胆固醇量的分子机制以及身体选择性排除其他膳食固醇的能力知之甚少。对罕见的常染色体隐性遗传性疾病谷固醇血症（OMIM 210250）的研究可能会对这些过程有所启发。患有这种疾病的患者似乎从肠道过度吸收胆固醇和植物甾醇。此外，肝脏优先和快速地将这些非胆固醇固醇排泄到胆汁中的能力失败。因此，患有这种疾病的人血浆植物甾醇水平非常高，并发展肌腱和结节性黄瘤，加速动脉粥样硬化和过早的冠状动脉疾病。因此，这种基因缺陷的鉴定可能会揭示净膳食胆固醇吸收的调节，并导致这一重要的心血管危险因素的管理进展。通过研究10个具有良好特征的患有这种疾病的家族，我们将遗传缺陷定位于染色体2p21，微卫星标记D2S1788和D2S1352之间（最大lodscore 4.49，θ = 0.0）。
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).