Melioidosis, infection caused by the Gram-negative bacterium Burkholderia 
pseudomallei, is a common cause of sepsis in northeast Thailand. In white North 
Americans, common functional genetic variation in TLR1 is associated with organ 
failure and death from sepsis. We hypothesized that TLR1 variants would be 
associated with outcomes in Thais with melioidosis. We collated the global 
frequencies of three TLR1 variants that are common in white North American 
populations: rs5743551 (-7202A/G), rs4833095 (742A/G), and rs5743618 (1804G/T). 
We noted a reversal of the minor allele from white North American subjects to 
Asian populations that was particularly pronounced for rs5743618. In the Utah 
residents of European ancestry, the frequency of the rs5743618 T allele was 17% 
whereas in Vietnamese subjects the frequency was >99%. We conducted a genetic 
association study in 427 patients with melioidosis to determine the association 
of TLR1 variation with organ failure or death. We genotyped rs5743551 and 
rs4833095. The variants were in high linkage disequilibrium but neither variant 
was associated with organ failure or in-hospital death. In 300 healthy Thai 
individuals we further tested the association of TLR1 variation with ex vivo 
blood responses to Pam3CSK4, a TLR1 agonist. Neither variant was robustly 
associated with blood cytokine responses induced by Pam3CSK4. We identified 
additional common variation in TLR1 by searching public databases and the 
published literature and screened three additional TLR1 variants for 
associations with Pam3CSK4-induced responses but found none. We conclude that 
the genetic architecture of TLR1 variation differs substantially in southeast 
Asians compared to other populations and common variation in TLR1 in Thais is 
not associated with outcome from melioidosis or with altered blood responses to 
Pam3CSK4. Our findings highlight the need for additional studies of TLR1 and 
other innate immune genetic modulators of the inflammatory host response and 
determinants of sepsis in southeast Asian populations.