Identification of a variant associated with adult-type hypolactasia

Abstract

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-persistence. 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 phenotype. 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.

Low prevalence of lactase persistence in Neolithic South-West Europe

“…4 The T allele, dominant over the C allele, has been described to be the allele associated with lactase persistence in European populations. 5 In other populations, different polymorphisms in the LCT promoter have been also shown to be associated with lactase persistence. 6 Several studies support the perspective that these differences in lactase persistence between populations can be ascribed to processes of positive selection.…”

RNA-Seq and human complex diseases: recent accomplishments and future perspectives

“…73 The association between nucleotide variants in a regulatory element of LCT gene and the lactase persistence phenotype in European population, identified about 10 years ago, 74 is one of the first -and perhaps better-knowndemonstration of this hypothesis. Since then, GWAS have unequivocally shown that SNPs affect gene expression.…”

Associations of the lactase persistence allele and lactose intake with body composition among multiethnic children

“…The ''T'' variant disrupts this binding motif and allows lactase production to occur at a rapid pace. Thus, the presence of a ''T'' variant is associated with unhindered gene transcription and lactase production, whereas a homozygous genotype for the ''C'' variant is associated with dysfunctional lactase production which results in lactose intolerance (Enattah et al 2002;Olds and Sibley 2003).…”