Skip to main content
Top
Published in: Malaria Journal 1/2011

Open Access 01-12-2011 | Research

Lactase persistence genotypes and malaria susceptibility in Fulani of Mali

Authors: A Inkeri Lokki, Irma Järvelä, Elisabeth Israelsson, Bakary Maiga, Marita Troye-Blomberg, Amagana Dolo, Ogobara K Doumbo, Seppo Meri, Ville Holmberg

Published in: Malaria Journal | Issue 1/2011

Login to get access

Abstract

Background

Fulani are a widely spread African ethnic group characterized by lower susceptibility to Plasmodium falciparum, clinical malaria morbidity and higher rate of lactase persistence compared to sympatric tribes. Lactase non-persistence, often called lactose intolerance, is the normal condition where lactase activity in the intestinal wall declines after weaning. Lactase persistence, common in Europe, and in certain African people with traditions of raising cattle, is caused by polymorphisms in the enhancer region approximately 14 kb upstream of the lactase gene.

Methods

To evaluate the relationship between malaria and lactase persistence genotypes, a 400 bp region surrounding the main European C/T-13910 polymorphism upstream of the lactase gene was sequenced. DNA samples used in the study originated from 162 Fulani and 79 Dogon individuals from Mali.

Results

Among 79 Dogon only one heterozygote of the lactase enhancer polymorphism was detected, whereas all others were homozygous for the ancestral C allele. Among the Fulani, the main European polymorphism at locus C/T-13910 was by far the most common polymorphism, with an allele frequency of 37%. Three other single-nucleotide polymorphisms were found with allele frequencies of 3.7%, 1.9% and 0.6% each. The novel DNA polymorphism T/C-13906 was seen in six heterozygous Fulani. Among the Fulani with lactase non-persistence CC genotypes at the C/T-13910 locus, 24% had malaria parasites detectable by microscopy compared to 18% for lactase persistent genotypes (P = 0.29). Pooling the lactase enhancer polymorphisms to a common presumptive genotype gave 28% microscopy positives for non-persistent and 17% for others (P = 0.11).

Conclusions

Plasmodium falciparum parasitaemia in asymptomatic Fulani is more common in individuals with lactase non-persistence genotypes, but this difference is not statistically significant. The potential immunoprotective properties of dietary cow milk as a reason for the partial malaria resistance of Fulani warrant further investigation.
Appendix
Available only for authorised users
Literature
1.
go back to reference Bersaglieri T, Sabeti PC, Patterson N, Vanderploeg T, Schaffner SF, Drake JA, Rhodes M, Reich DE, Hirschhorn JN: Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet. 2004, 74: 1111-1120.PubMedCentralCrossRefPubMed Bersaglieri T, Sabeti PC, Patterson N, Vanderploeg T, Schaffner SF, Drake JA, Rhodes M, Reich DE, Hirschhorn JN: Genetic signatures of strong recent positive selection at the lactase gene. Am J Hum Genet. 2004, 74: 1111-1120.PubMedCentralCrossRefPubMed
2.
3.
go back to reference Tishkoff SA, Reed FA, Ranciaro A, Voight BF, Babbitt CC, Silverman JS, Powell K, Mortensen HM, Hirbo JB, Osman M: Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet. 2007, 39: 31-40.PubMedCentralCrossRefPubMed Tishkoff SA, Reed FA, Ranciaro A, Voight BF, Babbitt CC, Silverman JS, Powell K, Mortensen HM, Hirbo JB, Osman M: Convergent adaptation of human lactase persistence in Africa and Europe. Nat Genet. 2007, 39: 31-40.PubMedCentralCrossRefPubMed
4.
go back to reference Enattah NS, Trudeau A, Pimenoff V, Maiuri L, Auricchio S, Greco L, Rossi M, Lentze M, Seo JK, Rahgozar S: Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans. Am J Hum Genet. 2007, 81: 615-625.PubMedCentralCrossRefPubMed Enattah NS, Trudeau A, Pimenoff V, Maiuri L, Auricchio S, Greco L, Rossi M, Lentze M, Seo JK, Rahgozar S: Evidence of still-ongoing convergence evolution of the lactase persistence T-13910 alleles in humans. Am J Hum Genet. 2007, 81: 615-625.PubMedCentralCrossRefPubMed
5.
go back to reference Ransome-Kuti O, Kretchmer N, Johnson JD, Gribble JT: A genetic study of lactose digestion in Nigerian families. Gastroenterology. 1975, 68: 431-436.PubMed Ransome-Kuti O, Kretchmer N, Johnson JD, Gribble JT: A genetic study of lactose digestion in Nigerian families. Gastroenterology. 1975, 68: 431-436.PubMed
6.
go back to reference Sahi T: Genetics and epidemiology of adult-type hypolactasia. Scand J Gastroenterol Suppl. 1994, 202: 7-20.CrossRefPubMed Sahi T: Genetics and epidemiology of adult-type hypolactasia. Scand J Gastroenterol Suppl. 1994, 202: 7-20.CrossRefPubMed
7.
go back to reference Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Jarvela I: Identification of a variant associated with adult-type hypolactasia. Nat Genet. 2002, 30: 233-237.CrossRefPubMed Enattah NS, Sahi T, Savilahti E, Terwilliger JD, Peltonen L, Jarvela I: Identification of a variant associated with adult-type hypolactasia. Nat Genet. 2002, 30: 233-237.CrossRefPubMed
8.
go back to reference Imtiaz F, Savilahti E, Sarnesto A, Trabzuni D, Al-Kahtani K, Kagevi I, Rashed MS, Meyer BF, Jarvela I: The T/G 13915 variant upstream of the lactase gene (LCT) is the founder allele of lactase persistence in an urban Saudi population. J Med Genet. 2007, 44: e89-PubMedCentralCrossRefPubMed Imtiaz F, Savilahti E, Sarnesto A, Trabzuni D, Al-Kahtani K, Kagevi I, Rashed MS, Meyer BF, Jarvela I: The T/G 13915 variant upstream of the lactase gene (LCT) is the founder allele of lactase persistence in an urban Saudi population. J Med Genet. 2007, 44: e89-PubMedCentralCrossRefPubMed
9.
go back to reference Ingram CJ, Elamin MF, Mulcare CA, Weale ME, Tarekegn A, Raga TO, Bekele E, Elamin FM, Thomas MG, Bradman N, Swallow DM: A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?. Hum Genet. 2007, 120: 779-788.CrossRefPubMed Ingram CJ, Elamin MF, Mulcare CA, Weale ME, Tarekegn A, Raga TO, Bekele E, Elamin FM, Thomas MG, Bradman N, Swallow DM: A novel polymorphism associated with lactose tolerance in Africa: multiple causes for lactase persistence?. Hum Genet. 2007, 120: 779-788.CrossRefPubMed
10.
go back to reference Torniainen S, Freddara R, Routi T, Gijsbers C, Catassi C, Hoglund P, Savilahti E, Jarvela I: Four novel mutations in the lactase gene (LCT) underlying congenital lactase deficiency (CLD). BMC Gastroenterol. 2009, 9: 8-PubMedCentralCrossRefPubMed Torniainen S, Freddara R, Routi T, Gijsbers C, Catassi C, Hoglund P, Savilahti E, Jarvela I: Four novel mutations in the lactase gene (LCT) underlying congenital lactase deficiency (CLD). BMC Gastroenterol. 2009, 9: 8-PubMedCentralCrossRefPubMed
11.
go back to reference Bryceson AD, Fleming AF, Edington GM: Splenomegaly in Northern Nigeria. Acta Trop. 1976, 33: 185-214.PubMed Bryceson AD, Fleming AF, Edington GM: Splenomegaly in Northern Nigeria. Acta Trop. 1976, 33: 185-214.PubMed
12.
go back to reference Dolo A, Modiano D, Maiga B, Daou M, Dolo G, Guindo H, Ba M, Maiga H, Coulibaly D, Perlman H: Difference in susceptibility to malaria between two sympatric ethnic groups in Mali. Am J Trop Med Hyg. 2005, 72: 243-248.PubMed Dolo A, Modiano D, Maiga B, Daou M, Dolo G, Guindo H, Ba M, Maiga H, Coulibaly D, Perlman H: Difference in susceptibility to malaria between two sympatric ethnic groups in Mali. Am J Trop Med Hyg. 2005, 72: 243-248.PubMed
13.
go back to reference Vafa M, Maiga B, Berzins K, Hayano M, Bereczky S, Dolo A, Daou M, Arama C, Kouriba B, Farnert A: Associations between the IL-4 -590 T allele and Plasmodium falciparum infection prevalence in asymptomatic Fulani of Mali. Microbes Infect. 2007, 9: 1043-1048.CrossRefPubMed Vafa M, Maiga B, Berzins K, Hayano M, Bereczky S, Dolo A, Daou M, Arama C, Kouriba B, Farnert A: Associations between the IL-4 -590 T allele and Plasmodium falciparum infection prevalence in asymptomatic Fulani of Mali. Microbes Infect. 2007, 9: 1043-1048.CrossRefPubMed
14.
go back to reference Vafa M, Israelsson E, Maiga B, Dolo A, Doumbo OK, Troye-Blomberg M: Relationship between immunoglobulin isotype response to Plasmodium falciparum blood stage antigens and parasitological indexes as well as splenomegaly in sympatric ethnic groups living in Mali. Acta Trop. 2009, 109: 12-16.CrossRefPubMed Vafa M, Israelsson E, Maiga B, Dolo A, Doumbo OK, Troye-Blomberg M: Relationship between immunoglobulin isotype response to Plasmodium falciparum blood stage antigens and parasitological indexes as well as splenomegaly in sympatric ethnic groups living in Mali. Acta Trop. 2009, 109: 12-16.CrossRefPubMed
15.
go back to reference Israelsson E, Ekstrom M, Nasr A, Dolo A, Kearsley S, Arambepola G, Homann MV, Maiga B, Doumbo OK, Elghazali G: Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa. Malar J. 2009, 8: 136-PubMedCentralCrossRefPubMed Israelsson E, Ekstrom M, Nasr A, Dolo A, Kearsley S, Arambepola G, Homann MV, Maiga B, Doumbo OK, Elghazali G: Marked differences in CRP genotype frequencies between the Fulani and sympatric ethnic groups in Africa. Malar J. 2009, 8: 136-PubMedCentralCrossRefPubMed
16.
go back to reference Torniainen S, Parker MI, Holmberg V, Lahtela E, Dandara C, Jarvela I: Screening of variants for lactase persistence/non-persistence in populations from South Africa and Ghana. BMC Genet. 2009, 10: 31-PubMedCentralCrossRefPubMed Torniainen S, Parker MI, Holmberg V, Lahtela E, Dandara C, Jarvela I: Screening of variants for lactase persistence/non-persistence in populations from South Africa and Ghana. BMC Genet. 2009, 10: 31-PubMedCentralCrossRefPubMed
17.
go back to reference Modiano D, Petrarca V, Sirima BS, Bosman A, Nebie I, Diallo D, Lamizana L, Esposito F, Coluzzi M: Plasmodium falciparum malaria in sympatric ethnic groups of Burkina Faso, west Africa. Parassitologia. 1995, 37: 255-259.PubMed Modiano D, Petrarca V, Sirima BS, Bosman A, Nebie I, Diallo D, Lamizana L, Esposito F, Coluzzi M: Plasmodium falciparum malaria in sympatric ethnic groups of Burkina Faso, west Africa. Parassitologia. 1995, 37: 255-259.PubMed
18.
go back to reference Modiano D, Petrarca V, Sirima BS, Nebie I, Diallo D, Esposito F, Coluzzi M: Different response to Plasmodium falciparum malaria in West African sympatric ethnic groups. P Natl Acad Sci USA. 1996, 93: 13206-13211.CrossRef Modiano D, Petrarca V, Sirima BS, Nebie I, Diallo D, Esposito F, Coluzzi M: Different response to Plasmodium falciparum malaria in West African sympatric ethnic groups. P Natl Acad Sci USA. 1996, 93: 13206-13211.CrossRef
19.
go back to reference Modiano D, Chiucchiuini A, Petrarca V, Sirima BS, Luoni G, Perlmann H, Esposito F, Coluzzi M: Humoral response to Plasmodium falciparum Pf155/ring-infected erythrocyte surface antigen and Pf332 in three sympatric ethnic groups of Burkina Faso. American Journal of Tropical Medicine and Hygiene. 1998, 58: 220-224.PubMed Modiano D, Chiucchiuini A, Petrarca V, Sirima BS, Luoni G, Perlmann H, Esposito F, Coluzzi M: Humoral response to Plasmodium falciparum Pf155/ring-infected erythrocyte surface antigen and Pf332 in three sympatric ethnic groups of Burkina Faso. American Journal of Tropical Medicine and Hygiene. 1998, 58: 220-224.PubMed
20.
go back to reference Modiano D, Petrarca V, Sirima BS, Luoni G, Nebie I, Diallo DA, Esposito F, Coluzzi M: Different response to Plasmodium falciparum in west African sympatric ethnic groups: possible implications for malaria control strategies. Parassitologia. 1999, 41: 193-197.PubMed Modiano D, Petrarca V, Sirima BS, Luoni G, Nebie I, Diallo DA, Esposito F, Coluzzi M: Different response to Plasmodium falciparum in west African sympatric ethnic groups: possible implications for malaria control strategies. Parassitologia. 1999, 41: 193-197.PubMed
21.
go back to reference Torcia MG, Santarlasci V, Cosmi L, Clemente A, Maggi L, Mangano VD, Verra F, Bancone G, Nebie I, Sirima BS: Functional deficit of T regulatory cells in Fulani, an ethnic group with low susceptibility to Plasmodium falciparum malaria. Proc Natl Acad Sci USA. 2008, 105: 646-651.PubMedCentralCrossRefPubMed Torcia MG, Santarlasci V, Cosmi L, Clemente A, Maggi L, Mangano VD, Verra F, Bancone G, Nebie I, Sirima BS: Functional deficit of T regulatory cells in Fulani, an ethnic group with low susceptibility to Plasmodium falciparum malaria. Proc Natl Acad Sci USA. 2008, 105: 646-651.PubMedCentralCrossRefPubMed
22.
go back to reference Bereczky S, Dolo A, Maiga B, Hayano M, Granath F, Montgomery SM, Daou M, Arama C, Troye-Blomberg M, Doumbo OK, Farnert A: Spleen enlargement and genetic diversity of Plasmodium falciparum infection in two ethnic groups with different malaria susceptibility in Mali, West Africa. Trans R Soc Trop Med Hyg. 2006, 100: 248-257.CrossRefPubMed Bereczky S, Dolo A, Maiga B, Hayano M, Granath F, Montgomery SM, Daou M, Arama C, Troye-Blomberg M, Doumbo OK, Farnert A: Spleen enlargement and genetic diversity of Plasmodium falciparum infection in two ethnic groups with different malaria susceptibility in Mali, West Africa. Trans R Soc Trop Med Hyg. 2006, 100: 248-257.CrossRefPubMed
23.
go back to reference McCall MB, Hopman J, Daou M, Maiga B, Dara V, Ploemen I, Nganou-Makamdop K, Niangaly A, Tolo Y, Arama C: Early interferon-gamma response against Plasmodium falciparum correlates with interethnic differences in susceptibility to parasitemia between sympatric Fulani and Dogon in Mali. J Infect Dis. 2010, 201: 142-152.CrossRefPubMed McCall MB, Hopman J, Daou M, Maiga B, Dara V, Ploemen I, Nganou-Makamdop K, Niangaly A, Tolo Y, Arama C: Early interferon-gamma response against Plasmodium falciparum correlates with interethnic differences in susceptibility to parasitemia between sympatric Fulani and Dogon in Mali. J Infect Dis. 2010, 201: 142-152.CrossRefPubMed
24.
go back to reference Vafa M, Maiga B, Israelsson E, Dolo A, Doumbo OK, Troye-Blomberg M: Impact of the IL-4 -590 C/T transition on the levels of Plasmodium falciparum specific IgE, IgG, IgG subclasses and total IgE in two sympatric ethnic groups living in Mali. Microbes Infect. 2009, 11: 779-784.CrossRefPubMed Vafa M, Maiga B, Israelsson E, Dolo A, Doumbo OK, Troye-Blomberg M: Impact of the IL-4 -590 C/T transition on the levels of Plasmodium falciparum specific IgE, IgG, IgG subclasses and total IgE in two sympatric ethnic groups living in Mali. Microbes Infect. 2009, 11: 779-784.CrossRefPubMed
25.
go back to reference Glew RH, Williams M, Conn CA, Cadena SM, Crossey M, Okolo SN, VanderJagt DJ: Cardiovascular disease risk factors and diet of Fulani pastoralists of northern Nigeria. Am J Clin Nutr. 2001, 74: 730-736.PubMed Glew RH, Williams M, Conn CA, Cadena SM, Crossey M, Okolo SN, VanderJagt DJ: Cardiovascular disease risk factors and diet of Fulani pastoralists of northern Nigeria. Am J Clin Nutr. 2001, 74: 730-736.PubMed
26.
go back to reference Rasinpera H, Savilahti E, Enattah NS, Kuokkanen M, Totterman N, Lindahl H, Jarvela I, Kolho KL: A genetic test which can be used to diagnose adult-type hypolactasia in children. Gut. 2004, 53: 1571-1576.PubMedCentralCrossRefPubMed Rasinpera H, Savilahti E, Enattah NS, Kuokkanen M, Totterman N, Lindahl H, Jarvela I, Kolho KL: A genetic test which can be used to diagnose adult-type hypolactasia in children. Gut. 2004, 53: 1571-1576.PubMedCentralCrossRefPubMed
29.
go back to reference Kicska GA, Ting LM, Schramm VL, Kim K: Effect of dietary p-aminobenzoic acid on murine Plasmodium yoelii infection. J Infect Dis. 2003, 188: 1776-1781.CrossRefPubMed Kicska GA, Ting LM, Schramm VL, Kim K: Effect of dietary p-aminobenzoic acid on murine Plasmodium yoelii infection. J Infect Dis. 2003, 188: 1776-1781.CrossRefPubMed
30.
go back to reference Chirico G, Marzollo R, Cortinovis S, Fonte C, Gasparoni A: Antiinfective properties of human milk. J Nutr. 2008, 138: 1801S-1806S.PubMed Chirico G, Marzollo R, Cortinovis S, Fonte C, Gasparoni A: Antiinfective properties of human milk. J Nutr. 2008, 138: 1801S-1806S.PubMed
32.
go back to reference Meloni T, Colombo C, Ogana A, Mannazzu MC, Meloni GF: Lactose absorption in patients with glucose 6-phosphate dehydrogenase deficiency with and without favism. Gut. 1996, 39: 210-213.PubMedCentralCrossRefPubMed Meloni T, Colombo C, Ogana A, Mannazzu MC, Meloni GF: Lactose absorption in patients with glucose 6-phosphate dehydrogenase deficiency with and without favism. Gut. 1996, 39: 210-213.PubMedCentralCrossRefPubMed
34.
go back to reference Auricchio S: Lactase deficiency phenotype has not been selected by malaria. Ital J Gastroenterol Hepatol. 1998, 30: 494-495.PubMed Auricchio S: Lactase deficiency phenotype has not been selected by malaria. Ital J Gastroenterol Hepatol. 1998, 30: 494-495.PubMed
35.
go back to reference Murray MJ, Murray AB, Murray NJ, Murray MB: Diet and cerebral malaria: the effect of famine and refeeding. Am J Clin Nutr. 1978, 31: 57-61.PubMed Murray MJ, Murray AB, Murray NJ, Murray MB: Diet and cerebral malaria: the effect of famine and refeeding. Am J Clin Nutr. 1978, 31: 57-61.PubMed
36.
go back to reference Murray J, Murray A, Murray M, Murray C: The biological suppression of malaria: an ecological and nutritional interrelationship of a host and two parasites. Am J Clin Nutr. 1978, 31: 1363-1366.PubMed Murray J, Murray A, Murray M, Murray C: The biological suppression of malaria: an ecological and nutritional interrelationship of a host and two parasites. Am J Clin Nutr. 1978, 31: 1363-1366.PubMed
37.
go back to reference Khabarova YTS, Savilahti E, Isokoski M, Mattila KJ, Jarvela I: The G/A-13914 variant upstream of the lactase gene (LCT) is a novel variant associated with lactase persistence/non persistence. Scand J Clin Lab Invest. Khabarova YTS, Savilahti E, Isokoski M, Mattila KJ, Jarvela I: The G/A-13914 variant upstream of the lactase gene (LCT) is a novel variant associated with lactase persistence/non persistence. Scand J Clin Lab Invest.
Metadata
Title
Lactase persistence genotypes and malaria susceptibility in Fulani of Mali
Authors
A Inkeri Lokki
Irma Järvelä
Elisabeth Israelsson
Bakary Maiga
Marita Troye-Blomberg
Amagana Dolo
Ogobara K Doumbo
Seppo Meri
Ville Holmberg
Publication date
01-12-2011
Publisher
BioMed Central
Published in
Malaria Journal / Issue 1/2011
Electronic ISSN: 1475-2875
DOI
https://doi.org/10.1186/1475-2875-10-9

Other articles of this Issue 1/2011

Malaria Journal 1/2011 Go to the issue
Obesity Clinical Trial Summary

At a glance: The STEP trials

A round-up of the STEP phase 3 clinical trials evaluating semaglutide for weight loss in people with overweight or obesity.

Developed by: Springer Medicine

Highlights from the ACC 2024 Congress

Year in Review: Pediatric cardiology

Watch Dr. Anne Marie Valente present the last year's highlights in pediatric and congenital heart disease in the official ACC.24 Year in Review session.

Year in Review: Pulmonary vascular disease

The last year's highlights in pulmonary vascular disease are presented by Dr. Jane Leopold in this official video from ACC.24.

Year in Review: Valvular heart disease

Watch Prof. William Zoghbi present the last year's highlights in valvular heart disease from the official ACC.24 Year in Review session.

Year in Review: Heart failure and cardiomyopathies

Watch this official video from ACC.24. Dr. Biykem Bozkurt discusses last year's major advances in heart failure and cardiomyopathies.