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Medical AI Inquiry: You was designed to assist in medical decision-making based on the provided user questions. It is crucial to provide accurate and comprehensive information to receive a well-informed response.  Labels: OBJECTIVE, METHODS, RESULTS. Meshes: Caco-2 Cells, Enhancer Elements, Genetic, HeLa Cells, Humans, Lactase-Phlorizin Hydrolase, Lactose Intolerance, Polymorphism, Genetic, Promoter Regions, Genetic, Sucrase-Isomaltase Complex.
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Does an upstream polymorphism associated with lactase persistence have increased enhancer activity? Context: Intestinal lactase activity declines during childhood in some humans. This phenotypic polymorphism of lactase persistence or nonpersistence into adult life has been shown in a recent study to be 100% associated with a T/C nucleotide polymorphism at position -13910 and approximately 97% with an A/G nucleotide polymorphism at position -22018. The aim of this study was to investigate the role of these nucleotide polymorphisms for lactase-phlorizin hydrolase (LPH) gene expression. The -13910 and -22018 regions were cloned from lactase-persistent and -nonpersistent individuals, and the regions were analyzed for gene regulatory activity of a luciferase reporter gene by transfection experiments using the intestinal cell line Caco-2. Electrophoretic mobility shift assays (EMSAs) were used to investigate protein/DNA interactions with the -13910 sequence. We show that the -13910 region contains a strong enhancer. The -13910 regions from both lactase persistent (-13910T variant) and lactase nonpersistent (-13910C variant) have enhancer activity. However, the -13910T variant enhances the LPH promoter approximately 4 times more than the -13910C variant when analyzed in differentiated Caco-2 cells. A nuclear factor from both an intestinal and a nonintestinal extract binds strongly to the -13910T variant whereas the binding to the -13910C variant is much weaker.
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The discovery of a functional difference between the 2 alleles at position -13910 supports the notion that the molecular difference between lactase persistence and nonpersistence is caused by the mutation at position -13910. Final Decision: yes