The T/G-13915 variant upstream of the lactase gene (LCT) is the founder allele of lactase persistence in an urban Saudi population

Background: The prevalence of lactase persistence is high in Saudi Arabia. Objective: To identify a DNA variant for the lactase persistence/non- persistence trait in adult Arabs in Saudi Arabia. Methods: We sequenced DNA from 432 anonymous neonatal blood donors from five different regions of Saudi Arabia to cover the 400 bp region surrounding the previously identified lactase persistence/non- persistence variant C/T-13910 residing in intron 13 of the MCM6 gene. Results: Two anonymous blood donors carried the C/T-13910 genotype. One variant, T/G-13915, residing 5 bp upstream of the C/T-13910 variant, was present in 332 of 432 (76.9%) of the neonatal samples, compatible with previous prevalence figures of lactase persistence in urban Saudi populations. Determination of disaccharidase activities in 25 intestinal biopsy samples showed a highly significant correlation between lactase activity and the T/G213915 genotypes (p, 0.001; Fisher exact test) as well as between the L: S ratio and the aforementioned genotypes (p, 0.001; Fisher exact test). Conclusion: The T/G213915 variant is the founder mutation of lactase persistence in an urban Saudi population. The results obtained here have implications for genetic testing of adult- type hypolactasia and to analysis of human evolution, the origin of cattle domestication and migrations of the populations in the Arabian peninsula.