P0066 PP GENETIC TESTING OF ADULT-TYPE HYPOLACTASIA

Abstract

Introduction: Adult-type hypolactasia affects most of world’s human population and limits the use of fresh milk due to lactose intolerance. The diagnosis of adult-type hypolactasia has been difficult to establish due to unsatisfactory diagnostic methods. We have identified a DNA variant residing 13910 bp upstream of the lactase-phlorizin hydrolase (LPH) gene at chromosome 2q21–22 that shows complete association with lactase non-persistence/persistence trait (Enattah 2002, Kuokkanen 2003). The genotype C/C-13910 is associated with adult-type hypolactasia and genotypes C/T-13910 and T/T-13910 with lactase persistence. We have assessed the applicability of the C/T-13910 variant as a diagnostic test at the time of downregulation of the lactase activity in children of African, Finnish and other Caucasian origins. Methods: Intestinal biopsies were obtained from 333 children and adolescents aged from 0.1 to 20 years undergoing upper gastrointestinal endoscopy because of unspecified abdominal complaints. The biopsies were assayed for lactase, sucrase and maltase activity and genotyped for the C/T-13910 variant using PCR-minisequencing (Messer 1966, Syvänen 1994). Results: The prevalence of the genotype C/C-13910 defining adult-type hypolactasia was 14.5% among Finnish (n=256), 95.4% among African (n=65) and 75.0% among the other Caucasian children (n=12). The majority of Finnish children (92%) with C/C-13910 genotype had high lactase activity (>10 U/g protein) before the age of five years. A gradual decline took place between 5–12 years of age. The decline of the lactase activity in African children occurred somewhat earlier than in Finnish children as 30% of the children already had low levels (<10 U/g protein) at the age of five years. In Finnish children with C/C-13910 genotype the probability of low lactase activity (<10 U/g protein) was 8% before five years of age, 63% between 6–11 years of age and 100% after 12 years of age. The C/C-13910 genotype was associated with low lactase activity (<10 U/g protein) in all children >12 years of age in all ethnic groups studied giving a sensitivity of 94% and specificity of 100% for this genetic test defining adult-type hypolactasia. Conclusion: Genetic testing of adult-type hypolactasia is a clinical aid in diagnosis of abdominal complaints in populations like those of Northern Europeans where the prevalence of adult-type hypolactasia is relatively high and consumption of dairy products common. This test is easily performed with a semiautomated analysis from a drop of peripheral blood without fasting making this test suitable not just for diagnostic purposes at individual level but also as a screening method for population studies. Reference(S):