Nature Genetics
30, 233 - 237 (2002)
Published online: 14 January 2002; | doi:10.1038/ng826
Identification of a variant associated with adult-type hypolactasiaNabil Sabri Enattah1, Timo Sahi2, Erkki Savilahti3, Joseph D. Terwilliger4, Leena Peltonen1, 5
& Irma Järvelä1, 61
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.
Correspondence should be addressed to lpeltonen@mednet.ucla.eduAdult-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.
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