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Toll-like receptors (TLRs) are cellular innate immune receptors that explore microbial molecules. For instance, TLR4 can sense bacterial lipopolysaccharides (LPS) inducing cytokines and anti-microbial peptides against the bacteria. It has been shown that single nucleotide polymorphisms (SNPs) in TLR4 are associated with diseases such as septic shock. Therefore, investigations of common SNPs may help to explain the pathogenesis of diseases and various innate immune responses against infections. This study investigates genotypic frequencies of two common TLR4 SNPs (Asp299Gly and Thr399Ile) in a Kurdish population using Restriction Length Fragment Polymorphisms (RFLP). Furthermore, the global frequencies of both TLR4 SNPs are reviewed in different populations of Sub-Saharan Africa, North Africa, Western Asia, Eurasia and East Asia and used to infer human migrations and past settlements. The RFLP data demonstrate that, in the Kurdish population, the genotypic frequencies of both SNPs are similar to Iranian or other Western Asian populations, which in turn are comparable to Eurasian populations suggesting past admixture due to migrations, population intermixing and common ancestry. The reviewed data reveal that the frequencies of the homozygous wild-types of TLR4 variants are prevalent, but homozygous mutants are rare or lacking in almost all global populations. Frequencies of the heterozygotes varied from population to others. For instance, in Sub-Saharan Africa the frequency of the Asp299Gly SNP is higher than Thr399Ile, whereas in the Arabic peninsula both SNPs are present at higher frequencies. In contrast, East Asian populations lack or have very low frequencies of both TLR4 SNPs of interest. Moreover, co-segregations of the TLR4 SNPs were common in some populations that may indicate their important roles in association with certain diseases. Future studies are required to link the TLR4 SNPs with either resistances against or susceptibility to diseases.