Sibley Eric, Ahn Jong Kun
Department of Pediatrics, Division of Gastroenterology, Hepatology and Nutrition Stanford University School of Medicine, 300 Pasteur Drive, G310, Stanford, CA 94305, USA.
Trans Am Clin Climatol Assoc. 2011;122:155-65.
Lactase-phlorizin hydrolase, lactase, is the intestinal enzyme responsible for the digestion of the milk sugar lactose. The majority of the world's human population experiences a decline in expression of the lactase gene by late childhood (lactase non-persistence). Individuals with lactase persistence, however, continue to express high levels of the lactase gene throughout adulthood. Lactase persistence is a heritable autosomal dominant condition and has been strongly correlated with several single nucleotide polymorphisms (SNPs) located ∼14 kb upstream of the lactase gene in different ethnic populations: -13910T in Europeans and -13907G, -13915G, and -14010C in several African populations. The coincidence of the four SNPs clustering within 100 bp strongly suggests that this region mediates the lactase non-persistence/persistence phenotype. Having previously characterized the European SNP, we aimed to determine whether the African SNPs similarly mediate a functional role in regulating the lactase promoter. Human intestinal Caco-2 cells were transfected with lactase SNP/promoter-reporter constructs and assayed for promoter activity. The -13907G and -13915G SNPs result in a significant enhancement of lactase promoter activity relative to the ancestral lactase non-persistence genotype. Such differential regulation by the SNPs is consistent with a causative role in the mechanism specifying the lactase persistence phenotype.
乳糖酶 - 根皮苷水解酶，即乳糖酶，是负责消化乳糖这种乳类糖分的肠道酶。世界上大多数人口在童年后期乳糖酶基因的表达会下降（乳糖酶不持续性）。然而，具有乳糖酶持续性的个体在成年期仍持续高水平表达乳糖酶基因。乳糖酶持续性是一种可遗传的常染色体显性性状，并且在不同种族人群中，它与位于乳糖酶基因上游约14 kb处的几个单核苷酸多态性（SNP）密切相关：欧洲人群中的 -13910T以及几个非洲人群中的 -13907G、-13915G和 -14010C。这四个SNP在100 bp范围内聚集的巧合强烈表明该区域介导了乳糖酶不持续性/持续性表型。在先前对欧洲SNP进行了特征描述之后，我们旨在确定非洲的这些SNP是否同样在调节乳糖酶启动子中发挥功能作用。用乳糖酶SNP/启动子 - 报告基因构建体转染人肠道Caco - 2细胞，并检测启动子活性。相对于祖传的乳糖酶不持续性基因型，-13907G和 -13915G这两个SNP导致乳糖酶启动子活性显著增强。SNP的这种差异调节与在决定乳糖酶持续性表型的机制中起因果作用是一致的。
