02142nas a2200205   4500000000100000008004100001653001200042653001700054653002500071100002000096700001600116700001400132700001300146700001100159700001500170700001600185700001700201245012200218520159600340       2013                            d10aleprosy10aPolymorphism10aCase-Control Studies1 aSuryadevara N C1 aNeela V S K1 aKovvali S1 aPydi S S1 aJain S1 aSiva Sai K1 aValluri V L1 aSpurgeon A M00aGenetic association of G896A polymorphism of TLR4 gene in leprosy through family-based and case-control study designs3 aBackground 
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 and Results 
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. 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. 

Conclusion 
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.