Evolutionary genetics of lactase persistence in Italy.

The enzyme that hydrolyzes lactose, the main carbohydrate in milk, is lactase-phlorizin hydrolase (LCT), which is encoded by the gene LCT located on chromosome 2. Normally, in all mammals, the ability to digest lactose rapidly declines after weaning, but in some human populations this ability persists in adulthood, a condition called lactase persistence (LP) (Swallow, 2003). Studies of the prevalence of the LP phenotype in worldwide populations have shown that the frequency of this trait is highly variable in different ethnic groups and appears to be positively correlated with the importance of the milk in the diet (Ingram et al., 2009). Several polymorphisms in the proximity of the LCT gene have been proved to be associated with LP phenotype. The first and the most important polymorphism was identified by Enattah et al. (2002), being located 13,910 base pairs 5’ of the start codon of LCT (-13,910*C/T) and being completely associated with LP in individuals of Finnish origin. In 2004, Bersaglieri et al. typed 101 single-nucleotide polymorphisms (SNPs) covering 3.2 Mb around the lactase gene. They demonstrated the presence of a common haplotype that extends largely undisrupted for >1 Mb in populations of northern European origins, confirming that this region of the human genome was recently subjected to a strong positive selection (Bersaglieri et al. 2004). According to these evidences, the aim of the project is to analyze the frequency spectrum of a panel of 51 SNPs selected on the basis of their highest heterozigosity values among those observed in the European subsample analyzed in Bersaglieri’s work. The sample is composed by 380 Italian healthy subjects distributed in six different macro-areas: North- Eastern, North-Western, Central-Eastern, Central-Western and Southern Italy, as well as Sicily and Sardinia. The project aims to be the first work that analyzes a so large numbers of SNPs potentially related to LP phenotype, in a wide and very wellcharacterized sample of Italian subjects. Genotyping on each study participant will be performed using the iPLEX Gold technology (Jurinke et al. 2002) and the MassARRAY DNA analysis with MALDI-TOF mass spectrometry (Sequenom, Inc., San Diego, CA). Preliminary results show a high variability in Italy with a long region of linkage disequilibrium around the - 13910*C/T variant in the North Italian subsamples.