title: Genetic association of G896A polymorphism of TLR4 gene in leprosy through family-based and case-control study designs.
abstract: BACKGROUND
  Polymorphisms in TLR4 may change the function of the protein and alter the efficiency of immune response of host to infection. The high relevance of host gene polymorphisms with outcome of Mycobacterium leprae infection led us to study the genetic association of TLR4 G896A polymorphism in order to identify its risk among contacts of affected leprosy patients.
  
  
  METHODS
  For case-control study design a total of 628 individuals were recruited; 17 multicase leprosy families which included 32 case-parent trios were considered for family-based study. Genotyping was done using PCR-RFLP method.
  
  
  RESULTS
  In case-control study AA genotype was positively associated while GA genotype was negatively associated with leprosy. In family based transmission disequilibrium test (TDT) analysis allele G was found to be over transmitted to the affected individuals.
  
  
  CONCLUSIONS
  Case-control study suggests that homozygous AA genotype may confer susceptibility and heterozygous GA genotype may confer resistance to leprosy, while allele A was observed to increase risk and that of allele G may confer resistance to leprosy. No strong transmission disequilibrium was detected in family-based TDT analysis, possibly due to lower number of trios. In contrast to case-control data allele G was over transmitted to the affected ones in TDT analysis. To conclude, the frequencies of genotypes in household contacts were almost the same as in leprosy patients, suggesting that contacts with AA genotype may be at higher risk of leprosy and may therefore require prophylactic inputs.
authors.affiliation: LEPRA India-Blue Peter Public Health & Research Centre, Cherlapally, Hyderabad 501301, India.
authors.forename: Naveen Chandra
authors.initials: NC
authors.lastname: Suryadevara
authors.forename: Venkata Sanjeev Kumar
authors.initials: VS
authors.lastname: Neela
authors.forename: Srinivas
authors.initials: S
authors.lastname: Kovvali
authors.forename: Satya Sudheer
authors.initials: SS
authors.lastname: Pydi
authors.forename: Suman
authors.initials: S
authors.lastname: Jain
authors.forename: K S R
authors.initials: KS
authors.lastname: Siva Sai
authors.forename: Vijaya Lakshmi
authors.initials: VL
authors.lastname: Valluri
authors.forename: Anandaraj M P J
authors.initials: AM
authors.lastname: Spurgeon
mesh_terms: D016022:Case-Control Studies; D005192:Family Health; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005838:Genotype; D006801:Humans; D007194:India / Q000453:epidemiology; D007918:Leprosy / Q000235:genetics* / Q000276:immunology; D016133:Polymerase Chain Reaction; D012150:Polymorphism, Restriction Fragment Length; D051197:Toll-Like Receptor 4 / Q000235:genetics*
chemical_list: D051197:Toll-Like Receptor 4
keywords: Contacts; Leprosy; PCR-RFLP; Polymorphism; TLR4