Tumor necrosis factor and lymphotoxin-alpha polymorphisms and severe malaria in African populations.

The tumor necrosis factor gene (TNF) and lymphotoxin-alpha gene (LTA) have long attracted attention as candidate genes for susceptibility traits for malaria, and several of their polymorphisms have been found to be associated with severe malaria (SM) phenotypes. In a large study involving >10,000 individuals and encompassing 3 African populations, we found evidence to support the reported associations between the TNF -238 polymorphism and SM in The Gambia. However, no TNF/LTA polymorphisms were found to be associated with SM in cohorts in Kenya and Malawi. It has been suggested that the causal polymorphisms regulating the TNF and LTA responses may be located some distance from the genes. Therefore, more-detailed mapping of variants across TNF/LTA genes and their flanking regions in the Gambian and allied populations may need to be undertaken to find any causal polymorphisms.

[1]  Pardis C Sabeti,et al.  Allelic heterogeneity of G6PD deficiency in West Africa and severe malaria susceptibility , 2009, European Journal of Human Genetics.

[2]  D. Kwiatkowski,et al.  Assessing Genuine Parents-Offspring Trios for Genetic Association Studies , 2008, Human Heredity.

[3]  C. Pipper,et al.  [''R"--project for statistical computing]. , 2008, Ugeskrift for laeger.

[4]  Meenakshi Singh,et al.  Stepwise replication identifies a low-producing lymphotoxin-α allele as a major risk factor for early-onset leprosy , 2007, Nature Genetics.

[5]  K. Tokunaga,et al.  Significant association between TNF-alpha (TNF) promoter allele (-1031C, -863C, and -857C) and cerebral malaria in Thailand. , 2007, Tissue antigens.

[6]  D. Kwiatkowski,et al.  Mendelian and complex genetics of susceptibility and resistance to parasitic infections. , 2006, Seminars in immunology.

[7]  S. Ranque,et al.  Alleles 308A and 238A in the Tumor Necrosis Factor Alpha Gene Promoter Do Not Increase the Risk of Severe Malaria in Children with Plasmodium falciparum Infection in Mali , 2006, Infection and Immunity.

[8]  Lon Cardon,et al.  Lymphotoxin-α Gene and Risk of Myocardial Infarction in 6,928 Cases and 2,712 Controls in the ISIS Case-Control Study , 2006, PLoS genetics.

[9]  F. Iraqi,et al.  TNF as a malaria candidate gene: polymorphism-screening and family-based association analysis of mild malaria attack and parasitemia in Burkina Faso , 2005, Genes and Immunity.

[10]  D. Kwiatkowski,et al.  Analysis of IL10 haplotypic associations with severe malaria , 2005, Genes and Immunity.

[11]  D. Kwiatkowski.  How malaria has affected the human genome and what human genetics can teach us about malaria. , 2005, American journal of human genetics.

[12]  C. Saiz-Jimenez,et al.  Multiple displacement amplification as a pre-polymerase chain reaction (pre-PCR) to process difficult to amplify samples and low copy number sequences from natural environments. , 2005, Environmental microbiology.

[13]  O. Migita,et al.  Haplotype analysis of a 100 kb region spanning TNF–LTA identifies a polymorphism in the LTA promoter region that is associated with atopic asthma susceptibility in Japan , 2005, Clinical and experimental allergy : journal of the British Society for Allergy and Clinical Immunology.

[14]  Julian C. Knight,et al.  Regulatory polymorphisms underlying complex disease traits , 2005, Journal of Molecular Medicine.

[15]  P. Rosenthal,et al.  Host polymorphisms and the incidence of malaria in Ugandan children. , 2004, The American journal of tropical medicine and hygiene.

[16]  T. Ottenhoff,et al.  Is there a future for TNF promoter polymorphisms? , 2004, Genes and Immunity.

[17]  I. Clark,et al.  Pathogenesis of Malaria and Clinically Similar Conditions , 2004, Clinical Microbiology Reviews.

[18]  D. Kwiatkowski,et al.  Dissection of class III major histocompatibility complex haplotypes associated with rheumatoid arthritis. , 2004, Arthritis and rheumatism.

[19]  D. Kwiatkowski,et al.  Allele-specific repression of lymphotoxin-α by activated B cell factor-1 , 2004, Nature Genetics.

[20]  J. Hampe,et al.  Patterns of linkage disequilibrium in the MHC region on human chromosome 6p , 2004, Human Genetics.

[21]  R. Mott,et al.  Complex haplotypic structure of the central MHC region flanking TNF in a West African population , 2003, Genes and Immunity.

[22]  N. Laird,et al.  Estimation and Tests of Haplotype-Environment Interaction when Linkage Phase Is Ambiguous , 2003, Human Heredity.

[23]  R. Nagel,et al.  Human genetic polymorphisms and asymptomatic Plasmodium falciparum malaria in Gabonese schoolchildren. , 2003, The American journal of tropical medicine and hygiene.

[24]  A. Mr.  Severe and complicated malaria. , 2002 .

[25]  P. Kaye,et al.  Locally Up-regulated Lymphotoxin α, Not Systemic Tumor Necrosis Factor α, Is the Principle Mediator of Murine Cerebral Malaria , 2002, The Journal of experimental medicine.

[26]  D. Schaid,et al.  Score tests for association between traits and haplotypes when linkage phase is ambiguous. , 2002, American journal of human genetics.

[27]  M. Aidoo,et al.  Tumor necrosis factor‐α promoter variant 2 (TNF2) is associated with pre‐term delivery, infant mortality, and malaria morbidity in western Kenya: Asembo Bay Cohort Project IX , 2001, Genetic epidemiology.

[28]  K. Tokunaga,et al.  Lack of association of -308A/G TNFA promoter and 196R/M TNFR2 polymorphisms with disease severity in Thai adult malaria patients. , 2001, American journal of medical genetics.

[29]  Warwick J. Britton,et al.  Secreted Lymphotoxin-α Is Essential for the Control of an Intracellular Bacterial Infection , 2001, The Journal of experimental medicine.

[30]  F. Migot-Nabias,et al.  Human genetic factors related to susceptibility to mild malaria in Gabon , 2000, Genes and Immunity.

[31]  Kevin Marsh,et al.  A polymorphism that affects OCT-1 binding to the TNF promoter region is associated with severe malaria , 1999, Nature Genetics.

[32]  Marcel Tanner,et al.  Malaria infection and morbidity in infants in relation to genetic polymorphisms in Tanzania , 1999, Tropical medicine & international health : TM & IH.

[33]  K. Mendis,et al.  TNFα*2 marks high risk of severe disease during Plasmodium falciparum malaria and other infections in Sri Lankans , 1999, Clinical and experimental immunology.

[34]  P. Ross,et al.  High level multiplex genotyping by MALDI-TOF mass spectrometry , 1998, Nature Biotechnology.

[35]  R. Snow,et al.  Indicators of life-threatening malaria in African children. , 1995, The New England journal of medicine.

[36]  D. Kwiatkowski,et al.  Variation in the TNF-α promoter region associated with susceptibility to cerebral malaria , 1994, Nature.

[37]  W. Ewens,et al.  Transmission test for linkage disequilibrium: the insulin gene region and insulin-dependent diabetes mellitus (IDDM). , 1993, American journal of human genetics.

[38]  R. Hubert,et al.  Whole genome amplification from a single cell: implications for genetic analysis. , 1992, Proceedings of the National Academy of Sciences of the United States of America.

[39]  B. M. Greenwood,et al.  TNF concentration in fatal cerebral, non-fatal cerebral, and uncomplicated Plasmodium falciparum malaria , 1990, The Lancet.

[40]  M. Molyneux,et al.  Tumor necrosis factor and disease severity in children with falciparum malaria. , 1989, The New England journal of medicine.

[41]  D. Kwiatkowski,et al.  Severe malarial anemia and cerebral malaria are associated with different tumor necrosis factor promoter alleles. , 1999, The Journal of infectious diseases.