Population Genetics of Lactase Persistence and Lactose Intolerance

BACKGROUND: Adult assimilation of lactose divides humans into dominant lactase-persistent and recessive nonpersistent phenotypes.OBJECTIVES: To review three medical parameters of lactose digestion, namely: the changing concept of lactose intolerance; the possible impact on diseases of microbial adaptation in lactase-nonpersistent populations; and the possibility that the evolution of lactase has influenced some disease pattern distributions.METHODS: A PubMed, Google Scholar and manual review of articles were used to provide a narrative review of the topic.RESULTS: The concept of lactose intolerance is changing and merging with food intolerances. Microbial adaptation to regular lactose consumption in lactase-nonpersistent individuals is supported by limited evidence. There is evidence suggestive of a relationship among geographical distributions of latitude, sunhine exposure and lactase proportional distributions worldwide.DISCUSSION: The definition of lactose intolerance has shifted away from association with lactose maldigestion. Lactose sensitivity is described equally in lactose digesters and maldigesters. The important medical consequence of withholding dairy foods could have a detrimental impact on several diseases; in addition, microbial adaptation in lactase-nonpersistent populations may alter risk for some diseases. There is suggestive evidence that the emergence of lactase persistence, together with human migrations before and after the emergence of lactase persistence, have impacted modern-day diseases.CONCLUSIONS: Lactose maldigestion and lactose intolerance are not synonymous. Withholding dairy foods is a poor method to treat lactose intolerance. Further epidemiological work could shed light on the possible effects of microbial adaptation in lactose maldigesters. The evolutionary impact of lactase may be still ongoing.

Download Full-text

Comparison of Quick Lactose Intolerance Test in duodenal biopsies of dyspeptic patients with single nucleotide polymorphism LCT-13910C>T associated with primary hypolactasia/lactase-persistence

Acta Cirurgica Brasileira ◽

10.1590/s0102-86502013001300015 ◽

2013 ◽

Vol 28 (suppl 1) ◽

pp. 77-82 ◽

Cited By ~ 1

Author(s):

Rejane Mattar ◽

Anibal Basile-Filho ◽

Rafael Kemp ◽

José Sebastião dos Santos

Keyword(s):

Lactose Intolerance ◽

Genetic Test ◽

Lactase Persistence ◽

Upper Gastrointestinal Endoscopy ◽

Polymorphism Analysis ◽

Kappa Index ◽

Quick Test ◽

Pcr Product ◽

Highly Sensitive ◽

Duodenal Biopsies

PURPOSE: To analyze the usefulness of Quick Lactose Intolerance Test in relation to the genetic test based on LCT-13910C>T genotypes, previously validated for clinical practice, for primary hypolactasia/lactase-persistence diagnosis. METHODS: Thirty-two dyspeptic patients that underwent upper gastrointestinal endoscopy entered the study. Two postbulbar duodenal biopsies were taken for the Quick test, and gastric antral biopsy for DNA extraction and LCT-13910C>T polymorphism analysis. DNA was also extracted from biopsies after being used in the Quick Test that was kept frozen until extraction. RESULTS: Nine patients with lactase-persistence genotype (LCT-13910CT or LCT-13910TT) had normolactasia, eleven patients with hypolactasia genotype (LCT-13910CC) had severe hypolactasia, and among twelve with mild hypolactasia, except for one that had LCT-13910CT genotype, all the others had hypolactasia genotype. The agreement between genetic test and quick test was high (p<0.0001; Kappa Index 0.92). Most of the patients that reported symptoms with lactose-containing food ingestion had severe hypolactasia (p<0.05). Amplification with good quality PCR product was also obtained with DNA extracted from biopsies previously used in the Quick Test; thus, for the future studies antral gastric biopsies for genetic test would be unnecessary. CONCLUSION: Quick test is highly sensitive and specific for hypolactasia diagnosis and indicated those patients with symptoms of lactose intolerance.

Download Full-text

Assessment of lactase activity in humans by measurement of galactitol and galactonate in serum and urine after milk intake

American Journal of Clinical Nutrition ◽

10.1093/ajcn/nqy296 ◽

2019 ◽

Vol 109 (2) ◽

pp. 470-477 ◽

Cited By ~ 1

Author(s):

Nathalie Vionnet ◽

Linda H Münger ◽

Carola Freiburghaus ◽

Kathryn J Burton ◽

Grégory Pimentel ◽

...

Keyword(s):

Lactose Intolerance ◽

Dairy Product ◽

Primary Objective ◽

Lactase Persistence ◽

Common Condition ◽

Lactase Activity ◽

Galactose Metabolism ◽

Lactose Maldigestion ◽

Genetically Determined ◽

Serum And Urine

ABSTRACT Background Lactase is an enzyme that hydrolyzes lactose into glucose and galactose in the small intestine, where they are absorbed. Hypolactasia is a common condition, primarily caused by genetic programming, that leads to lactose maldigestion and, in certain cases, lactose intolerance. Galactitol and galactonate are 2 products of hepatic galactose metabolism that are candidate markers for the intake of lactose-containing foods. Objectives The primary objective of the study was to explore the changes in serum and urine metabolomes during postprandial dairy product tests through the association between lactase persistence genotype and the postprandial dynamics of lactose-derived metabolites. Methods We characterized the 6-h postprandial serum kinetics and urinary excretion of lactose, galactose, galactitol, and galactonate in 14 healthy men who had consumed a single dose of acidified milk (800 g) which contained 38.8 g lactose. Genotyping of LCT-13910 C/T (rs4988235) was performed to assess primary lactase persistence. Results There were 2 distinct postprandial responses, classified as high and low metabolite responses, observed for galactose, and its metabolites galactitol and galactonate, in serum and urine. In all but 1 subject, there was a concordance between the high metabolite responses and genetic lactase persistence and between the low metabolite responses and genetic lactase nonpersistence (accuracy 0.92), galactitol and galactonate being more discriminative than galactose. Conclusions Postprandial galactitol and galactonate after lactose overload appear to be good proxies for genetically determined lactase activity. The development of a noninvasive lactose digestion test based on the measurement of these metabolites in urine could be clinically useful. This trial was registered at clinicaltrials.gov as NCT02230345.

Download Full-text

Lactase persistence versus lactose intolerance: Is there an intermediate phenotype?

Clinical Biochemistry ◽

10.1016/j.clinbiochem.2015.11.001 ◽

2016 ◽

Vol 49 (3) ◽

pp. 248-252 ◽

Cited By ~ 15

Author(s):

Zbigniew Dzialanski ◽

Michael Barany ◽

Peter Engfeldt ◽

Anders Magnuson ◽

Lovisa A. Olsson ◽

...

Keyword(s):

Lactose Intolerance ◽

Lactase Persistence ◽

Intermediate Phenotype

Download Full-text

Tracing the Distribution of European Lactase Persistence Genotypes Along the Americas

Frontiers in Genetics ◽

10.3389/fgene.2021.671079 ◽

2021 ◽

Vol 12 ◽

Author(s):

Ana Cecília Guimarães Alves ◽

Natalie Mary Sukow ◽

Gabriel Adelman Cipolla ◽

Marla Mendes ◽

Thiago P. Leal ◽

...

Keyword(s):

Allele Frequency ◽

Dairy Products ◽

Lactose Intolerance ◽

Middle Eastern ◽

Dietary Guidelines ◽

Lactase Persistence ◽

Dominant Effect ◽

European Origin ◽

Pan American ◽

Flanking Region

In adulthood, the ability to digest lactose, the main sugar present in milk of mammals, is a phenotype (lactase persistence) observed in historically herder populations, mainly Northern Europeans, Eastern Africans, and Middle Eastern nomads. As the –13910∗T allele in the MCM6 gene is the most well-characterized allele responsible for the lactase persistence phenotype, the –13910C > T (rs4988235) polymorphism is commonly evaluated in lactase persistence studies. Lactase non-persistent adults may develop symptoms of lactose intolerance when consuming dairy products. In the Americas, there is no evidence of the consumption of these products until the arrival of Europeans. However, several American countries’ dietary guidelines recommend consuming dairy for adequate human nutrition and health promotion. Considering the extensive use of dairy and the complex ancestry of Pan-American admixed populations, we studied the distribution of –13910C > T lactase persistence genotypes and its flanking haplotypes of European origin in 7,428 individuals from several Pan-American admixed populations. We found that the –13910∗T allele frequency in Pan-American admixed populations is directly correlated with allele frequency of the European sources. Moreover, we did not observe any overrepresentation of European haplotypes in the –13910C > T flanking region, suggesting no selective pressure after admixture in the Americas. Finally, considering the dominant effect of the –13910∗T allele, our results indicate that Pan-American admixed populations are likely to have higher frequency of lactose intolerance, suggesting that general dietary guidelines deserve further evaluation across the continent.

Download Full-text

Genetic aspects of lactase persistence in different ethnic groups

Faktori eksperimental'noi evolucii organizmiv ◽

10.7124/feeo.v27.1324 ◽

2020 ◽

Vol 27 ◽

pp. 185-189

Author(s):

V. V. Borozenets ◽

V. O. Babalian ◽

O. M. Fedota

Keyword(s):

Statistical Analysis ◽

Ethnic Groups ◽

Medical Information ◽

Lactose Intolerance ◽

Lactase Persistence ◽

Spearman Correlation ◽

Adult Type ◽

Age Dependent ◽

High Degree ◽

Indian Students

Aim. The aim of this study was evaluation of the genetic aspects of lactase persistence (LP) in persons from different ethnic groups. Methods. Genealogical and medical information was collected about Ukrainian, Indian, Nigerian, Israel, Egypt, Palestine, Turkey, Jordan students (n=361) and their first degree relatives (n=413). Statistical analysis was carried out by Shapiro-Wilk test, χ2, Spearman correlation. Results. The phenotype of LP was found in 69.9 % of Ukrainians, lactose intolerance - in 7.2 %. The highest LP is observed in 95.2 % of Nigerians, the lowest - Palestinians, 51.9 %. Analysis in all ethnic groups showed that the number of LP people is less among parents than among students (r = - 0.529, p <0.05). The LP score is 72.7 - 95.2 % among Nigerian, Israeli, Egyptian, Turkish, Indian students, and 60 - 76.5 % among their parents. The LP phenotype is 50 – 68.8 % and 53.9 – 70.9 % among Ukrainian, Palestinian Jordanian students and their parents. It is likely that adult-type hypolactasia may appear after 20 years and older, indicating a high degree of heterozygosity. The highest number of persons with first exogamy degree is 82.6-85.5 % among Turks, Palestinians, Egyptians and the lowest value of LP phenotype is observed in these groups - 51.9 - 72.3 %, (r = – 0.786, p<0.05). A positive correlation is determined between the traits of hypolactasia and first degree of parents exogamy (r = 0.905, p<0.05). The changes in metabolic status with age could be a predictor for multifactorial pathology. Conclusions. Adult hypolactasia is an age-dependent trait. Relations between the parameters of LP and the origin were established. Keywords: lactase persistence, lactose intolerance, exogamy, genotypes.

Download Full-text