Kuchay Raja Amir Hassan
Department of Biotechnology, Baba Ghulam Shah Badshah University, Rajouri, J&K, India.
Drug Discov Ther. 2020 Mar 8;14(1):1-7. doi: 10.5582/ddt.2019.01079. Epub 2020 Feb 26.
Lactose, a disaccharide and main carbohydrate in milk, requires hydrolysis in the intestinal tract to release its monosaccharides galactose and glucose for use as energy source by enterocytes. This hydrolysis is catalyzed by the enzyme lactase, a β-galactosidase located in the brush border membrane of small intestinal enterocytes. In most mammals, lactase activity declines after the weaning, a condition known as lactase non-persistence (LNP). Lactase persistence (LP) is an autosomal dominant trait enabling the continued production of the enzyme lactase throughout adult life. Non-persistence or persistence of lactase expression into adult life being a polymorphic trait has been attributed to various single nucleotide polymorphisms in the enhancer region surrounding lactase gene (LCT). However, latest research has pointed to 'genetic-epigenetic interactions' as key to regulation of lactase expression. LNP and LP DNA haplotypes have demonstrated markedly different epigenetic aging as genetic factors contribute to gradual accumulation of epigenetic changes with age to affect lactase expression. This review will attempt to present an overview of latest insights into molecular basis of LNP/LP including the crucial role of 'genetic-epigenetic interactions' in regulating lactase expression.
乳糖是一种双糖，也是牛奶中的主要碳水化合物，它需要在肠道中水解，释放出单糖半乳糖和葡萄糖，以供肠细胞用作能量来源。这种水解作用由乳糖酶催化，乳糖酶是一种β-半乳糖苷酶，位于小肠肠细胞的刷状缘膜上。在大多数哺乳动物中，断奶后乳糖酶活性会下降，这种情况称为乳糖酶不持续性（LNP）。乳糖酶持续性（LP）是一种常染色体显性性状，可使乳糖酶在成年期持续产生。乳糖酶表达在成年期的不持续性或持续性作为一种多态性性状，已归因于乳糖酶基因（LCT）周围增强子区域的各种单核苷酸多态性。然而，最新研究指出“基因-表观遗传相互作用”是乳糖酶表达调控的关键。由于遗传因素会导致表观遗传变化随着年龄的增长逐渐积累，从而影响乳糖酶表达，LNP和LP DNA单倍型已显示出明显不同的表观遗传衰老。本综述将试图概述关于LNP/LP分子基础的最新见解，包括“基因-表观遗传相互作用”在调节乳糖酶表达中的关键作用。
