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Transcriptional regulation of the lactase-phlorizin hydrolase gene by polymorphisms associated with adult-type hypolactasia
  1. M Kuokkanen1,
  2. N S Enattah1,
  3. A Oksanen2,
  4. E Savilahti3,
  5. A Orpana4,
  6. I Järvelä4
  1. 1Department of Medical Genetics, University of Helsinki, Finland and National Public Health Institute, Department of Molecular Medicine, Helsinki, Finland
  2. 2Herttoniemi Hospital, Helsinki, Finland
  3. 3Hospital for Children and Adolescents, University of Helsinki, Finland
  4. 4Laboratory of Molecular Genetics, HUCH-Laboratory Diagnostics, Helsinki, Finland
  1. Correspondence to:
    Dr I Järvelä, PL 140, HUCH-Laboratory Diagnostics, Haartmaninkatu 2, 00029 Helsinki, Finland;


Background and aims: The mechanism of the developmental downregulation of the lactase-phlorizin hydrolase (LPH) gene underlying adult-type hypolactasia is unknown. We have determined the functional significance of the recently identified two single nucleotide polymorphisms (SNPs), C/T−13910 and G/A−22018, associated with adult-type hypolactasia by studying LPH mRNA levels in intestinal biopsy samples with different genotypes.

Methods: Intestinal biopsy samples were taken from 52 patients with abdominal complaints. Hypolactasia was diagnosed by determining lactase and sucrase activities and calculating their ratio (L/S ratio). The functional effect of the C/T−13910 and G/A−22018 genotype on expression of LPH mRNA was demonstrated in patients heterozygous for the C/T−13910 and G/A−22018 polymorphism and an informative expressed SNP located in the coding region of the LPH mRNA. Reverse transcription-polymerase chain reaction followed by solid phase minisequencing was used for accessing the relative expression levels of the LPH alleles using informative SNPs located in exons 1, 2, 6, 10, 13, or 17 as markers.

Results: Statistically significant differences between the three different genotypes CC−13910 GG−22018, CT−13910 GA−22018, and TT−13910 AA-22018 and their respective L/S ratios were observed. Relative quantitation of the expressed LPH alleles showed that the persistent allele represented 92 (6)% (mean (SEM), range 78–99%; n=14) of the expressed LPH mRNA. The patient with the homozygous persistent TT−13910 AA−22018, as well as hypolactasic patients with CC−13910 GG−22018, showed equal expression of both alleles (47 (1)%; n=7).

Conclusions: Expression of LPH mRNA in the intestinal mucosa in individuals with T−13910 A−22018 alleles is several times higher than that found in individuals with C−13910, G−22018 alleles. These findings suggest that the two SNPs, C/T−13910 and G/A−22018, associated with adult-type hypolactasia, are associated with the transcriptional regulation of the LPH gene. The presence of the T−13910 A−22018 allele also shows significant elevation of the L/S ratio.

  • adult-type hypolactasia
  • transcriptional regulation
  • lactase-phlorizin hydrolase gene
  • lactase-phlorizin hydrolase
  • polymorphism
  • LPH, lactase-phlorizin hydrolase
  • SNP, single nucleotide polymorphism
  • cSNP, coding region single nucleotide polymorphism
  • L/S ratio, lactase/sucrase ratio
  • RT-PCR, reverse transcription-polymerase chain reaction
  • dNTP, deoxynucleotide triphosphate

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