title: Tumour necrosis factor α polymorphism (TNF-308α G/A) in association with asthma related phenotypes and air pollutants among children in KwaZulu-Natal.
abstract: BACKGROUND
  The study of gene-environment interactions enables us to further understand the pathogenesis of asthma and inflammation. The TNF-α gene has been associated with airway pathology in asthma but there is limited information in relation to pollutant exposure and the TNF-α 308G/A polymorphism.
  
  
  OBJECTIVE
  To determine the risk conferred by the TNF-α 308(G/A) polymorphism on respiratory outcome and to evaluate whether the association between exposure to ambient air pollutants such as SO2, NO2, NO, and PM10 and variation in lung function measures is modified by genotype.
  
  
  METHODS
  The sample comprised 129 African children (between 9-11 years old). A questionnaire based on guidelines from the British Medical Research Council and the American Thoracic Society was administered to all caregivers to evaluate the prevalence of respiratory symptoms. Atopy was evaluated by skin prick testing. Bihourly measures of lung function (spirometry) were collected at school five days per week over three week periods in each of four seasons (2004-2005) using digital hand-held devices. During each of the four intensive 3-week phases, gaseous air pollutant concentrations were monitored continuously. Polymerase Chain Reaction-Restriction Fragment Length Polymorphism (PCR-PFLP) analysis was used to detect the TNF-α 308 genotype and plasma TNF-α levels were measured using the human TNF-α Max Standard™ Enzyme-linked immuno-absorbent assay (ELISA) kit.
  
  
  RESULTS
  The TNF-α variant A allele was common among this sample of African children (40% with an allelic frequency of 0.24). There was no significant association with the TNF-α G/A polymorphism and any respiratory linked phenotype, nor cytokine levels. However, when exposure to pollutants were analyzed with genotypic and phenotypic data, we found relatively modest interaction effects for the TNF-α 308 genotype. GEE models showed that children with the TNF-α 308 A allele had increased deterioration of lung function post pollution exposure to SO2 [β=2.62, CI:0.51-4.71, p=0.02 and pint=0.03] and NO [β=3.28, CI:0.68-5.89, p=0.01, pint=0.03].
  
  
  CONCLUSIONS
  The TNF-α 308 (G/A) polymorphism may be associated with increased pollutant-associated effects on FEV1 intraday variability for both SO2 and NO. The A allele may increase susceptibility to the adverse effects of air pollutants.
authors.affiliation: Department of Community Health Studies, Durban University of Technology, Durban, South Africa.
authors.forename: Michelle T
authors.initials: MT
authors.lastname: Makamure
authors.affiliation: Department of Community Health Studies, Durban University of Technology, Durban, South Africa.
authors.forename: Poovendhree
authors.initials: P
authors.lastname: Reddy
authors.affiliation: Discipline of Medical Biochemistry, School of Laboratory Medicine, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Anil
authors.initials: A
authors.lastname: Chuturgoon
authors.affiliation: Discipline of Occupational and Environmental Health, School of Nursing and Public Health, University of KwaZulu-Natal, Durban, South Africa.
authors.forename: Rajen N
authors.initials: RN
authors.lastname: Naidoo
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Graciela
authors.initials: G
authors.lastname: Mentz
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Stuart
authors.initials: S
authors.lastname: Batterman
authors.affiliation: Department of Environmental Health Sciences, University of Michigan, Ann Arbor, Michigan, USA.
authors.forename: Thomas G
authors.initials: TG
authors.lastname: Robins
mesh_terms: D000393:Air Pollutants / Q000009:adverse effects; D000397:Air Pollution / Q000009:adverse effects; D001249:Asthma / Q000235:genetics*; D002648:Child; D004781:Environmental Exposure / Q000009:adverse effects; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D059647:Gene-Environment Interaction; D020022:Genetic Predisposition to Disease / Q000235:genetics*; D006801:Humans; D008297:Male; D052638:Particulate Matter / Q000032:analysis; D010641:Phenotype; D012150:Polymorphism, Restriction Fragment Length; D020641:Polymorphism, Single Nucleotide; D012129:Respiratory Function Tests; D013019:South Africa / Q000453:epidemiology; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
chemical_list: D000393:Air Pollutants; D052638:Particulate Matter; D014409:Tumor Necrosis Factor-alpha