Robayo-Torres Claudia C, Nichols Buford L
Department of Pediatrics, Baylor College of Medicine, 1100 Bates St., Houston, TX 77030, USA.
Nutr Rev. 2007 Feb;65(2):95-8. doi: 10.1111/j.1753-4887.2007.tb00286.x.
A limited fraction of the human adult population retains intestinal lactase-phlorizin hydrolase (LPH) activity during adulthood, and this is called the lactase persistence phenotype. However, 95% of all adults have adult-type hypolactasia (ATH) and have difficulty digesting milk sugar. Rarely, some infants are born with an inability to digest lactase (congenital lactase deficiency or CLD) due to low levels of LPH activity, which results in severe clinical consequences if not properly diagnosed and treated by lactose avoidance. Recently, it has been shown that both recessive LPH deficiencies, CLD and ATH, are related to DNA variants affecting the lactase (LCT) gene, but they are mediated through very different molecular mechanisms. The LCT mutations resulting in childhood CLD lead to low LPH activity through nonsense-mediated LCT mRNA decay, whereas the critical nucleotide variants for the ATH phenotype represent distal enhancer polymorphisms, which regulate developmentally LCT transcript levels in intestinal cells.
在人类成年人群体中，仅有一小部分人在成年期仍保留肠道乳糖酶 - 根皮苷水解酶（LPH）活性，这被称为乳糖酶持续存在表型。然而，所有成年人中有95%患有成人型低乳糖酶症（ATH），消化乳糖存在困难。极少数情况下，一些婴儿由于LPH活性水平低而天生无法消化乳糖酶（先天性乳糖酶缺乏症或CLD），如果不通过避免乳糖摄入进行正确诊断和治疗，会导致严重的临床后果。最近研究表明，隐性LPH缺乏症，即CLD和ATH，均与影响乳糖酶（LCT）基因的DNA变异有关，但它们是通过非常不同的分子机制介导的。导致儿童CLD的LCT突变通过无义介导的LCT mRNA降解导致LPH活性降低，而ATH表型的关键核苷酸变异代表远端增强子多态性，其在发育过程中调节肠道细胞中LCT转录水平。
