A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?

Ingram, Catherine J. E.; Elamin, Mohamed F.; Mulcare, Charlotte A.; Weale, Michael E.; Tarekegn, Ayele; Oljira Raga, Tamiru; Bekele, Endashaw; Elamin, Farouk M.; Thomas, Mark G.; Bradman, Neil; Swallow, Dallas M.

Persistence or non-persistence of lactase expression into adult life is a polymorphic trait that has been attributed to a single nucleotide polymorphism ( C-13910T) in an enhancer element 13.9 kb upstream of the lactase gene ( LCT). The -13910*T allele occurs at very high frequency in northern Europeans as part of a very long haplotype (known as A), and promotes binding of the transcription factor Oct-1. However, -13910*T is at very low frequency in many African milk drinking pastoralist groups where lactase persistence phenotype has been reported at high frequency. We report here for the first time, a cohort study of lactose digester and non-digester Sudanese volunteers and show there is no association of -13910*T or the A haplotype with lactase persistence. We support this finding with new genotype/phenotype frequency comparisons in pastoralist groups of eastern African and Middle Eastern origin. Resequencing revealed three new SNPs in close proximity to -13910*T, two of which are within the Oct-1 binding site. The most frequent of these (- 13915*G) is associated with lactose tolerance in the cohort study, providing evidence for a cis-acting effect. Despite its location, - 13915*G abolishes, rather than enhances Oct-1 binding, indicating that this particular interaction is unlikely to be involved in lactase persistence. This study reveals the complexity of this phenotypic polymorphism and highlights the limitations of C-13910T as a diagnostic test for lactase persistence status, at least for people with non-European ancestry.

LACTASE persistence; LACTOSE intolerance; DISACCHARIDES; TRANSCRIPTION factors; GENETIC polymorphisms; PHENOTYPES

Human Genetics, 2007, Vol 120, Issue 6, p779

0340-6717

Academic Journal

10.1007/s00439-006-0291-1