Genetic testing for adult-type hypolactasia in Italian families

Adult-type hypolactasia is characterized by the inability to digest lactose during adulthood, due to lactase (LCT) deficiency. It is usually diagnosed by the measurement of breath hydrogen increase after a lactose load (breath hydrogen test). A substitution of C to T at position -13910 bp upstream the LCT gene (rs4988234), in a regulatory region, was found to be tightly associated with the Lactase Persistence phenotype in North-European populations. We have investigated the -13910 C/T polymorphism to determine LCT genotype distribution and to validate genetic testing for adult type hypolactasia in a Southern European population. 43 children referred for suspected lactose malabsorption, their parents and siblings (112 individuals), were submitted to breath test, clinical monitoring and genotype determination. 125 unrelated blood donors from the same geographic area were genotyped for the calculation of allelic frequencies. The frequency of C/C genotypes was 70%. The correlation between the C/C genotype (which should correspond to lactose non digesters) and positive BHT in unrelated family founders was statistically significant (chi2=16.7, p<0.002). The genetic test compared to BHT had a sensitivity of 95% and 91% and a specificity of 48% and 55% in adults and children, respectively. Low specificity might be due to intrinsic limitations of the standard BHT or to other possible mutations, although no sequence variation was found upon sequencing a 253 bp fragment of LCT regulatory region in asymptomatic individuals.