Skip to main content

Thank you for visiting nature.com. You are using a browser version with limited support for CSS. To obtain the best experience, we recommend you use a more up to date browser (or turn off compatibility mode in Internet Explorer). In the meantime, to ensure continued support, we are displaying the site without styles and JavaScript.

  • Original Article
  • Published:

Genetic testing improves the diagnosis of adult type hypolactasia in the Mediterranean population of Sardinia

Abstract

Objective:

Recently, the C/T-13910 polymorphism on chromosome 2q21 in North-European populations has been found completely associated with lactase activity and its genetic typing proposed as first-stage screening test for adult hypolactasia. However, the C/T-13910 variant in some sub-Saharan African groups is not a predictor of lactase persistence. In this work, we wanted to verify if in the Mediterranean island of Sardinia, located in Southern Europe, the C/T-13910 polymorphism may be useful or not for the diagnosis of adult type hypolactasia.

Design:

Validation study of a genetic testing for adult type hypolactasia in Sardinians.

Setting:

Brotzu Hospital and Microcitemico Hospital, Cagliari, Italy.

Subjects:

The sample consisted in 84 Sardinian individuals (63 women and 21 men; range 20–73 years) selected from a group of 832 patients.

Methods:

Genetic testing was compared to an improved test obtained by a combination of different breath hydrogen tests and clinical assessment.

Results:

We found that all 49 individuals with lactose malabsorption, demonstrated by a combination of different breath hydrogen tests and clinical assessment, carried the C/C-13910 genotype associated with lactase non-persistence, 23 individuals with lactose normal absorption carried the C/T-13910 genotype associated with lactase persistence and only one person with the above phenotype showed a discordant C/C-13910 genotype. The genetic testing showed very high sensitivity, specificity, positive and negative predictive values of 100, 95.8, 98 and 100%, respectively.

Conclusions:

Sardinians, unlike some ethnic groups in sub-Saharan Africa, show the same genetic association of hypolactasia with the C/T-13910 variant as other North-European populations. The genetic testing for the C/T-13910 variant may contribute to improving the diagnosis of adult type hypolactasia.

This is a preview of subscription content, access via your institution

Access options

Rent or buy this article

Prices vary by article type

from$1.95

to$39.95

Prices may be subject to local taxes which are calculated during checkout

Figure 1

Similar content being viewed by others

References

  • Bond Jr JH, Levitt MD (1972). Use of pulmonary hydrogen (H2) measurements to quantitate carbohydrate absorption. Study of partially gastrectomized patients. J Clin Invest 51, 1219–1225.

    Article  CAS  Google Scholar 

  • Brummer RJ, Karibe M, Stockbrugger RW (1993). Lactose malabsorption. Optimalization of investigational methods. Scand J Gastroenterol Suppl 200, 65–69.

    Article  CAS  Google Scholar 

  • Buning C, Ockenga J, Kruger S, Jurga J, Baier P, Dignass A et al. (2003). The C/C(−13910) and G/G(−22018) genotypes for adult-type hypolactasia are not associated with inflammatory bowel disease. Scand J Gastroenterol 38, 538–542.

    Article  Google Scholar 

  • Corazza GR, Strocchi A, Gasbarrini G (1987). Fasting breath hydrogen in celiac disease. Gastroenterology 93, 53–58.

    Article  CAS  Google Scholar 

  • Corazza G, Strocchi A, Sorge M, Bentai G, Gasbarrini G (1993). Prevalence and consistency of low breath H2 excretion following lactulose ingestion. Possible implications for the clinical use of the H2 breath test. Dig Dis Sci 38, 2010–2016.

    Article  CAS  Google Scholar 

  • Corazza GR, Benati G, Strocchi A, Malservisi S, Gasbarrini G (1994). The possible role of breath methane measurement in detecting carbohydrate malabsorption. J Lab Clin Med 124, 695–700.

    CAS  PubMed  Google Scholar 

  • Di Stefano M, Missanelli A, Miceli E, Mazzocchi S, Corazza G (2003). Evaluation of the accuracy of a portable device, gastrolyzer EC60 Bedfont, for hydrogen (H2) detection in expired air. Dig Liv Dis suppl 4, S63.

    Google Scholar 

  • Di Stefano M, Veneto G, Malservisi S, Strocchi A, Corazza GR (2001). Lactose malabsorption and intolerance in the elderly. Scand J Gastroenterol 36, 1274–1278.

    Article  CAS  Google Scholar 

  • Eidsvoll BE, Schjonsby H (1989). Hydrogen breath tests in the diagnosis of primary lactase deficiency]. Tidsskr Nor Laegeforen 109, 354–356.

    CAS  PubMed  Google Scholar 

  • Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Jarvela I (2002). Identification of a variant associated with adult-type hypolactasia. Nat Genet 30, 233–237.

    Article  CAS  Google Scholar 

  • Flatz G (1987). Genetics of lactose digestion in humans. Adv Hum Genet 16, 1–77.

    CAS  PubMed  Google Scholar 

  • Grand RJ, Montgomery RK, Chitkara DK, Hirschhorn JN (2003). Changing genes; losing lactase. Gut 52, 617–619.

    Article  CAS  Google Scholar 

  • Hermans MM, Brummer RJ, Ruijgers AM, Stockbrugger RW (1997). The relationship between lactose tolerance test results and symptoms of lactose intolerance. Am J Gastroenterol 92, 981–984.

    CAS  PubMed  Google Scholar 

  • Kozlov AI, Balanovskaia EV, Nurbaev SD, Balanovskii OP (1998). [Genogeographic primary hypolactasia in the Old World populations]. Genetika 34, 551–561.

    CAS  PubMed  Google Scholar 

  • Metz G, Jenkins DJ, Peters TJ, Newman A, Blendis LM (1975). Breath hydrogen as a diagnostic method for hypolactasia. Lancet 1, 1155–1157.

    Article  CAS  Google Scholar 

  • Miller SA, Dykes DD, Polesky HF (1988). A simple salting out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 16, 1215.

    Article  CAS  Google Scholar 

  • Montes RG, Perman JA (1991). Lactose intolerance. Pinpointing the source of nonspecific gastrointestinal symptoms. Postgrad Med 89, 175–178, 181–174.

    Article  CAS  Google Scholar 

  • Mulcare CA, Weale ME, Jones AL, Connell B, Zeitlyn D, Tarekegn A et al. (2004). The T allele of a single-nucleotide polymorphism 13 9 kb upstream of the lactase gene (LCT) (C-13.9kbT) does not predict or cause the lactase-persistence phenotype in Africans. Am J Hum Genet 74, 1102–1110.

    Article  CAS  Google Scholar 

  • Myles S, Bouzekri N, Haverfield E, Cherkaoui M, Dugoujon JM, Ward R (2005). Genetic evidence in support of a shared Eurasian-North African dairying origin. Hum Genet 117, 34–42.

    Article  Google Scholar 

  • Olds LC, Sibley E (2003). Lactase persistence DNA variant enhances lactase promoter activity in vitro: functional role as a cis regulatory element. Hum Mol Genet 12, 2333–2340.

    Article  CAS  Google Scholar 

  • Poulter M, Hollox E, Harvey CB, Mulcare C, Peuhkuri K, Kajander K et al. (2003). The causal element for the lactase persistence/non-persistence polymorphism is located in a 1 Mb region of linkage disequilibrium in Europeans. Ann Hum Genet 67, 298–311.

    Article  CAS  Google Scholar 

  • Rasinpera H, Savilahti E, Enattah NS, Kuokkanen M, Totterman N, Lindahl H et al. (2004). A genetic test which can be used to diagnose adult-type hypolactasia in children. Gut 53, 1571–1576.

    Article  CAS  Google Scholar 

  • Sahi T (1994). Genetics and epidemiology of adult-type hypolactasia. Scand J Gastroenterol Suppl 202, 7–20.

    Article  CAS  Google Scholar 

  • Simren M, Stotzer PO (2006). Use and abuse of hydrogen breath tests. Gut 55, 297–303.

    Article  CAS  Google Scholar 

  • Suarez FL, Adshead J, Furne JK, Levitt MD (1998). Lactose maldigestion is not an impediment to the intake of 1500 mg calcium daily as dairy products. Am J Clin Nutr 68, 1118–1122.

    Article  CAS  Google Scholar 

  • Swallow DM (2003). Genetics of lactase persistence and lactose intolerance. Annu Rev Genet 37, 197–219.

    Article  CAS  Google Scholar 

  • Troelsen JT, Olsen J, Moller J, Sjostrom H (2003). An upstream polymorphism associated with lactase persistence has increased enhancer activity. Gastroenterology 125, 1686–1694.

    Article  CAS  Google Scholar 

  • Veligati LN, Treem WR, Sullivan B, Burke G, Hyams JS (1994). Delta 10 ppm versus delta 20 ppm: a reappraisal of diagnostic criteria for breath hydrogen testing in children. Am J Gastroenterol 89, 758–761.

    CAS  PubMed  Google Scholar 

Download references

Author information

Authors and Affiliations

Authors

Corresponding author

Correspondence to M Congia.

Additional information

Guarantor: E Schirru.

Contributors: ES participated in the genotyping of the DNA variant, designing and drawing the paper and approved the final version. VC participated in the genotyping of the DNA variant, designing and drawing the paper and approved the final version. PUS participated in performing the breath test, in designing and drawing the paper and approved the final version. MS participated in performing the breath test and designing the paper approved the final version. FO participated in designing the paper and in collecting the bibliography and approved the final version. FLI participated in designing the paper and in selecting subjects negative and positive at the lactose breath hydrogen test with 25 g of lactose and approved the final version. FC participated in designing the paper and in statistical analysis and approved the final version. SDeV participated in designing the paper and in collecting the bibliography and approved the final version. RR participated in performing cloning, sequencing and designing the paper and approved the final version. MDM participated in performing cloning, sequencing and designing of the paper and approved the final version. RDJ participated in designing and drawing the paper and approved the final version. MC participated in genotyping the DNA, designing and drawing the paper and approved the final version.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Schirru, E., Corona, V., Usai-Satta, P. et al. Genetic testing improves the diagnosis of adult type hypolactasia in the Mediterranean population of Sardinia. Eur J Clin Nutr 61, 1220–1225 (2007). https://doi.org/10.1038/sj.ejcn.1602638

Download citation

  • Received:

  • Revised:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1038/sj.ejcn.1602638

Keywords

This article is cited by

Search

Quick links