Published online: 14 January 2002, DOI:10.1038/ng826


Identification of a variant associated with adult-type hypolactasia

Nabil Sabri Enattah1, Timo Sahi2, Erkki Savilahti3, Joseph D. Terwilliger4,
Leena Peltonen1, 5, 7 & Irma Järvelä1, 6


Adult-type hypolactasia, also known as lactase non-persistence (lactose
intolerance), is a common autosomal recessive condition resulting from the
physiological decline in activity of the lactase-phlorizin hydrolase (LPH)
in intestinal cells after weaning. LPH hydrolyzes lactose into glucose and
galactose. Sequence analyses of the coding and promoter regions of LCT, the
gene encoding LPH, has revealed no DNA variations correlating with lactase
non-persistence1, 2. An associated haplotype spanning LCT, as well as a
distinct difference in the transcript levels of 'non-persistence' and
'persistence' alleles in heterozygotes, suggest that a cis-acting element
contributes to the lactase non-persistence phenotype3, 4. Using linkage
disequilibrium (LD) and haplotype analysis of nine extended Finnish
families, we restricted the locus to a 47-kb interval on 2q21. Sequence
analysis of the complete region and subsequent association analyses revealed
that a DNA variant, C/T-13910, roughly 14 kb upstream from the LCT locus,
completely associates with biochemically verified lactase non-persistence in
Finnish families and a sample set of 236 individuals from four different
populations. A second variant, G/A-22018, 8 kb telomeric to C/T-13910, is
also associated with the trait in 229 of 236 cases. Prevalence of the
C/T-13910 variant in 1,047 DNA samples is consistent with the reported
prevalence of adult-type hypolactasia in four different populations. That
the variant (C/T-13910) occurs in distantly related populations indicates
that it is very old.



1. Department of Molecular Medicine, National Public Health Institute,
Haartmaninkatu 8, PO Box 104, FIN-00251 Helsinki; and Department of Medical
Genetics, University of Helsinki, Finland.
2. Department of Public Health, University of Helsinki.
3. Hospital for Children and Adolescents, University of Helsinki, Helsinki,
Finland.
4. Department of Psychiatry and Columbia Genome Center, Columbia University,
New York, New York, USA; and Division of Medical Genetics, New York State
Psychiatric Institute, New York, New York, USA.
5. Department of Human Genetics, UCLA School of Medicine, Los Angeles,
California, USA.
6. HUCH-Laboratory Diagnostics, Laboratory of Molecular Genetics,
Haartmanninkatu 2, PO Box 340, FIN-00290 Helsinki, Finland.
7.
Correspondence should be addressed to L Peltonen. e-mail:
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