The Regulatory Mechanism Of-13838 G/A For Lactase Persistence In Tibetans

Lactose is an important component of fresh milk and dairy product.The digestion of lactose needs to be done with the involvement of intestinal lactase that is encoded by lactase gene(LCT).Lactase is present in the small intestine brush margin membrane and hydrolyzes lactose into galactose and glucose.For most people,the ability to digest lactose form dairy product,gradually declines after weaning because of decreasing levels of LCT.When taking dairy products with high levels of lcatose it is easy to occur abdominal pain,diarrhea and other lactose intolerance.However,the lactase persistence lasting into adulthood occurs in some 35% of humans worldwide.And these people are still able to digest lactose.Tibetan is an agricultural and pastoral ethnic group who has lived in the Tibetan plateau for a long time.Fresh milk and dairy products are important part s of their diet.Aprevious study revealed lower level of lactose intolerance in Tibetan than in Chinese Han populations,implying lactase persistence in Tibetans.The previously reported five single-nucleotide polymorphisms(SNPs)involving in lactase persistence are almost absent in Tibetan populations.Interestingly,the-13838*A allele has a higher frequency.We proposed it could be correlated with lactase persistence in Tibetans.To explore the regulatory mechanism of-13838G/A loci in the lactase persistence in the Tibetan population,we conducted functional experiments on cellular level.We found that-13838*A allele could significantly enhance LCT promoter activity compared to-13838*G allele from the double luciferase report experiment.The chromatin immunoprecipitation assay suggested that-13838G/A located at the binding site of the HNF-4? transcription factor.EMSA result confirmed that the binding ability of-13838*A allele was significantly stronger than that of-13838*G allele with the HNF-4?.Our results suggest-13838*A could increase LCT promoter activity by with the HNF-4?,and make controbutions to the lactase persistence in Tibetans.