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Harvey, C B*1; Wang, Y1; Phillips, A D2; Clay, P3; Johnson, A3; Walker-Smith, J A2; Swallow, D M1

Journal of Pediatric Gastroenterology & Nutrition: May 1996 - Volume 22 - Issue 4 - p 415
Annual Meeting of the European Society of Pediatric Gastroenterology and Nutrition

1MRC Human Biochemical Genetics Unit, University College, 2Paediatric Gastroenterology, Royal Free Hospital, 3Queen Elizabeth Hospital for Children, London, UK.

*Supported by the British Digestive Foundation

    The intestinal enzyme lactase is responsible for the digestion of lactose, the major carbohydrate in breast milk. In most mammals lactase activity declines after weaning; in contrast, in man lactase activity persists into adult life in about half the population. The persistence or non-persistence of lactase is genetically determined and we have shown that the critical DNA element determining lactase mRNA expression in adult life resides within, or close to, the lactase gene itself. The use of DNA marker polymorphisms within the lactase gene has shown mRNA transcription from only one lactase allele in some individuals; these individuals tend to have intermediate lactase activity and are thought to be heterozygotes carrying one lactase persistence allele and one lactase non-persistence allele.

    There is a variable age of onset for adult-type lactose intolerance. We have reviewed lactase activities in 319 small intestinal biopsies from children (aged 1-72 months) and found age-related changes in lactase activity. In order to pursue this further we have examined lactase mRNA expression and activity in 30 children (aged 4-144 months) in comparison to 14 fetuses (10-17 weeks) and our previously described series of 51 adults (aged 21-83 years). 29/30 children had normal small intestinal mucosal morphology, high lactase activity (which overlapped the high end of the range for the duodenum in lactase persistent adults) and high levels of lactase mRNA. 10 children were heterozygous for DNA marker polymorphisms and 4 of these (aged 18-132 months) expressed just one allele, presumably being lactase persistent heterozygotes with a switched off non-persistent allele. All the fetuses had low lactase activities and low lactase mRNA; 5 fetuses were heterozygous for DNA marker polymorphisms and expressed both alleles equally, like non-persistent adults.

    This genetic approach provides direct information on the timing of down-regulation of lactase gene expression, showing it can occur as early as the second year of life. These observations are relevant to elucidating of the underlying causes of the loss of lactase activity in children.

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    Munich, June 5-8, 1996

    © Lippincott-Raven Publishers