Information - Concepts In Nutrigenomics - Lactose Intolerance


The Molecular Explanation

Lactose intolerance (also known as lactase non-persistence or hypolactasia) is another excellent example of adverse genome/diet interactions. Lactose intolerance limits the use of fresh milk (and milk products) among adults and produces a painful digestive condition commonly associated with nausea, cramps bloating, gas, and diarrhea. Epidemiological data shown in the table indicate that the frequency of lactose intolerance varies widely depending on geography, age, race and ethnicity (Table 1).

Table 1
% Hypolactasia (lactose intolerance)*

Race, Ethnicity, Country of Origin


Southeast Asians


Asian Americans


Alaskan Eskimo


African-American Adults


Mexicans (rural communities)


North American Jews


Greek Cypriots




Mexican American Males


Indian Adults


African American Children


Indian Children


Descendents of N. Europeans


* Assembeled by R. Rodriguez 
from various sources

Recently, investigators have identified a genetic variant or SNP (C/T13910), 14kb upstream of the LCH (lactase-phlorizin hydrolase) locus on the large arm of human chromosome 2 (2q21). This variant, first identified in nine extended Finnish families, is responsible for lactose tolerance, (i.e., lactase persistence) or the ability for adults to consume fresh milk and milk products without complications. The polymorphism occurs in the promoter of the lactase gene and is thought to alter regulatory protein - DNA interactions controlling expression of the gene in adults. The 11 polymorphisms of this gene are clustered into 4 (A,B,C,U) prevalent (> 0.05%) haplotypes. The A haplotype conferring lactose tolerance has an 86% frequency in the northern European population, but only 36% in southern European populations. Cultures that drink fresh milk generally have a high er frequency of the A allele. The persistence of this gene in populations may confer selective advantages that include improved nutrition, prevention of dehydration, and improved calcium absorption.

The emergence of the lactase persistence variant is a relatively recent evolutionary event, appearing in Northern Europeans only 10,000 to 12,000 years ago (approximately with the time that animals were domesticated). The discovery of the C/T13910 DNA variant should now make it possible to design individualized dietary interventions based on a genetic test for lactose intolerance in early childhood. Genotype X environment (diet) interactions are uncomplicated when one allele or haplotype (i.e., a NAT2 allele or a lactase allele) is exposed to one xenobiotic (e.g., arylamine for NAT2) or dietary chemical (i.e., lactose for lactase). Enzyme activity is altered or the regulation of gene expression is changed.  

Further reading

Enattah, NS, Sahi, T, Savilahti, E, Terwillerger, JD, Peltonen, L., Jarvela, I. 2002.  Identification of a variant associated with adult-type hypolactasia. Nat Genet 30, 233-7. PMID: 11788828