-13915*G DNA polymorphism associated with lactase persistence in Africa interacts with Oct-1

Lactase gene expression declines with aging (lactase non-persistence) in the majority of humans worldwide. Lactase persistence is a heritable autosomal dominant condition and has been strongly correlated with several single nucleotide polymorphisms (SNPs) located similar to 14-kb upstream (-13907, -13910 and -13915) of the lactase gene in different ethnic populations. In contrast to the -13907*G and -13910*T SNPs, the -13915*G SNP was previously believed not to interact with Oct-1. In the present study, however, Oct-1 is shown to interact with the -13915*G SNP region DNA sequence by EMSAs and gel supershift. In addition, Oct-1 is capable of enhancing promoter activity of a lactase promoter-reporter construct harboring the -13915*G SNP sequence in cell culture. Oct-1 binding to the -13907 to -13915 SNP region therefore remains a candidate interaction involved in lactase persistence. 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 similar to 14-kb upstream of the lactase gene in different ethnic populations: -13910*T in Europeans and -13907*G, -13915*G, and -14010*C in several African ethnic pastoral populations (Enattah et al. 2002, 2008; Ingram et al. 2007; Tishkoff et al. 2007). Though strongly correlated with the lactase persistence phenotypes, a functional mechanism for the SNPs inmediating lactase persistence has not been clearly defined. Transfection experiments have shown that the lactase persistence SNP region DNA can function as a cis element capable of enhancing differential transcriptional activation of the lactase promoter in cell culture (Olds and Sibley 2003; Troelsen et al. 2003; Lewinsky et al. 2005). While previous reports have indicated that the -13907*G and -13910*T SNP region sequences can interact with the Oct-1 transcription factor (Lewinsky et al. 2005; Ingram et al. 2007), Oct-1 binding to the -13915*G SNP was minimal or not detected (Ingram et al. 2007; Enattah et al. 2008). In the present study, however, we demonstrate that the -13915*G region can interact with the Oct-1 protein.