Genotype Frequency of the Common TLR4 SNPs in a Kurdish Population: Global Reviews and Out-of-African Migrations

Toll-like receptors (TLRs) are cellular innate immune receptors that explore microbial molecules. For instance, TLR4 can sense bacterial lipopolysaccharides, inducing cytokines and antimicrobial peptides against the bacteria. Single-nucleotide polymorphisms (SNPs) in TLR4 are associated with diseases such as septic shock. Therefore, investigations of common SNPs may help explain the pathogenesis of diseases and various innate immune responses to infections. This study investigated genotypic frequencies of the two common TLR4 SNPs, Asp299Gly and Thr399Ile, in a Kurdish population using restriction length fragment polymorphisms (RFLPs). Global frequencies of both TLR4 SNPs in different populations of sub-Saharan Africa, North Africa, western Asia, Eurasia, and East Asia were also 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 West Asian populations, which in turn are comparable to Eurasian populations, suggesting past admixture due to migrations, population intermixing, and common ancestry. Globally, 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 among populations. For instance, in sub-Saharan Africa the frequency of the Asp299Gly SNP is higher than that of Thr399Ile, whereas in the Arabian Peninsula both SNPs are present at high frequencies. In contrast, East Asian populations lack or have very low frequencies of both TLR4 SNPs of interest. Moreover, co-segregation of the TLR4 SNPs is common in some populations, which may indicate important associations with certain diseases. Future studies are required to link the TLR4 SNPs with either resistance or susceptibility to diseases

An outbreak of Leishmania major from an endemic to a non-endemic region posed a public health threat in Iraq from 2014-2017: Epidemiological, molecular and phylogenetic studies.

Cutaneous leishmaniasis (CL) is a neglected worldwide, zoonotic, vector-borne, tropical disease that is a threat to public health. This threat may spread from endemic to non-endemic areas. Current research has exploited epidemiological, molecular and phylogenetical studies to determine the danger of an outbreak of CL in the borderline area between northern and central Iraq from 2014-2017.For the first time, using sequence analysis of the cytochrome b gene, the occurrence of CL in the borderline area between northern and central Iraq was confirmed to be due to Leishmania major. The phylogenetic analysis indicated that it was closely related to the L. major MRHO/IR/75/ER strain in Iran.In conclusion, the genotype confirmation of the L. major strain will improve our understanding of the epidemiology of the disease. This is important for facilitating control programs to prevent the further spread of CL. Furthermore, this area could be considered as a model for further research on the risk of global CL epidemics in other non-endemic countries where both reservoir hosts and sandfly vectors are present

Year-wise trend of the number of reported CL cases in Iraq.

<p>Data based on WHO reports for Iraq [<a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006255#pntd.0006255.ref015" target="_blank">15</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006255#pntd.0006255.ref016" target="_blank">16</a>, <a href="http://www.plosntds.org/article/info:doi/10.1371/journal.pntd.0006255#pntd.0006255.ref022" target="_blank">22</a>].</p

Monthly distribution of the number of reported CL cases in the Garmian region.

<p>Data were collected from reports of the Department of Transmissible Diseases of Garmian from 2014–2017.</p

Phylogenetic analysis of cytochrome <i>b</i> gene sequences among <i>Leishmania</i> species.

<p>The scale bar represents 0.01% divergence. Bootstrap values are shown above or below branches. Underlined GenBank accession numbers represent <i>L</i>. <i>major</i> sequences identified in this study.</p