title: Human lymphatic filariasis: genetic polymorphism of endothelin-1 and tumor necrosis factor receptor II correlates with development of chronic disease.
abstract: BACKGROUND
  Hydrocele and elephantiasis are 2 clinically very diverse and often mutually exclusive chronic manifestations of human bancroftian filariasis. Plasma levels of endothelin-1 (ET-1), a major angiogenic factor, and tumor necrosis factor receptors (TNFRs) that regulate host inflammation have been associated with development of chronic filariasis, although their genetic basis are not known.
  
  
  METHODS
  We studied polymorphisms of ET-1 (Ala288Ser) and TNFR-II (Met196Arg) genes by means of the polymerase chain reaction confronting 2 pairs primers method and restriction fragment length polymorphism, respectively. Plasma ET-1 level was measured by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Met196Arg genotype frequency of TNFR-II polymorphism was significantly greater in hydrocele patients, compared with elephantiasis patients (OR, 4.34 [95% CI, 2.04-9.20]). Conversely, a significantly high prevalence of the Ala288Ser mutation of ET-1 was observed in elephantiasis patients, compared with hydrocele cases (OR, 2.15 [95% CI, 1.13-4.10]). Decreased plasma ET-1 levels associated significantly with Ala288Ser mutation in the study population. A combined analysis indicated a 23-fold higher risk for developing elephantiasis in individuals with TNFR-II (Met196Met) and ET-1 mutants (Ala288Ser + Ser288Ser).
  
  
  CONCLUSIONS
  ET-1 (Ala288Ser) and TNFR-II (Met196Arg) polymorphisms are associated with development of one or the other form of chronic disease in bancroftian filariasis.
authors.affiliation: Divison of Immunology, Regional Medical Research Centre (ICMR), Chandrasekharpur, Bhubaneswar, Odisha, India.
authors.forename: Aditya Kumar
authors.initials: AK
authors.lastname: Panda
authors.forename: Prakash Kumar
authors.initials: PK
authors.lastname: Sahoo
authors.forename: Anna Solami
authors.initials: AS
authors.lastname: Kerketta
authors.forename: Santanu Kumar
authors.initials: SK
authors.lastname: Kar
authors.forename: Balachandran
authors.initials: B
authors.lastname: Ravindran
authors.forename: Ashok Kumar
authors.initials: AK
authors.lastname: Satapathy
mesh_terms: D000293:Adolescent; D000328:Adult; D019943:Amino Acid Substitution / Q000235:genetics; D002908:Chronic Disease; D017931:DNA Primers / Q000235:genetics; D004605:Elephantiasis, Filarial / Q000235:genetics*; D019332:Endothelin-1 / Q000097:blood / Q000235:genetics*; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D006801:Humans; D008297:Male; D008875:Middle Aged; D020125:Mutation, Missense; D016133:Polymerase Chain Reaction / Q000379:methods; D011110:Polymorphism, Genetic; D047889:Receptors, Tumor Necrosis Factor, Type II / Q000235:genetics*; D055815:Young Adult
chemical_list: D017931:DNA Primers; D019332:Endothelin-1; D047889:Receptors, Tumor Necrosis Factor, Type II