ReviewJournal of innate immunity2012
The evolutionary history of TLR4 polymorphisms in Europe.
Review in Journal of innate immunity, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers, 1 of them a synthesis that pooled it.
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Who cites it
12 citing papers in PubMed, 1 synthesis or guideline pooled it.
- Association between the -159C/T polymorphism in the promoter region of the CD14 gene and sepsis: a meta-analysis.BMC anesthesiology · 2017Pooled it
- Genetic variation in the prostaglandin E2 pathway is associated with primary graft dysfunction.American journal of respiratory and critical care medicine · 2014Trial
- Single Nucleotide Polymorphisms of Toll-like Receptor 4 in Hepatocellular Carcinoma-A Single-Center Study.International journal of molecular sciences · 2022Article
- Interaction of TLR4 and TLR8 in the Innate Immune Response against Mycobacterium Tuberculosis.International journal of molecular sciences · 2021Article
- Anti-inflammatory effects of Bifidobacterium longum subsp infantis secretions on fetal human enterocytes are mediated by TLR-4 receptors.American journal of physiology. Gastrointestinal and liver physiology · 2016Article
- The influence of genetic polymorphisms in TLR4 and TIRAP, and their expression levels in peripheral blood, on susceptibility to sepsis.Experimental and therapeutic medicine · 2016Article
- TLRs, SNPs and VLBWs: oh my!Journal of perinatology : official journal of the California Perinatal Association · 2013Article
- Report of four new patients with protein-truncating mutations in C6orf221/KHDC3L and colocalization with NLRP7.European journal of human genetics : EJHG · 2013Article
- Race and gender variation in response to evoked inflammation.Journal of translational medicine · 2013Article
- Inner ear tissue remodeling and ion homeostasis gene alteration in murine chronic otitis media.Otology & neurotology : official publication of the American Otological Society, American Neurotology Society [and] European Academy of Otology and Neurotology · 2013Article
- Variation in PTX3 is associated with primary graft dysfunction after lung transplantation.American journal of respiratory and critical care medicine · 2012Article
- Genetic variation in Toll-like receptors and disease susceptibility.Nature immunology · 2012Review
Corrections and comments
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Authors and funding
9 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Infections exert important evolutionary pressures shaping the human genome, especially on genes involved in host defense. A crucial step for host defense is recognition of pathogens by pattern recognition receptors on innate immune cells, among which Toll-like receptor 4 (TLR4) is one of the best known. Genetic variation in TLR4 (Asp299Gly, Thr399Ile) has been recently described. Haplotype frequencies of these polymorphisms differ among African, Asian and European populations, suggesting evolutionary pressures exerted by local infections. The TLR4 299Gly/399Ile haplotype, characteristic mainly of European populations, has relatively high frequency in the Iberian peninsula. This region is also described as refuge area during the last glacial maximum 20,000 years ago, from which repopulation of Europe took place. We speculate that a genetic bottleneck in the Iberian peninsula could have promoted the increased frequency of this haplotype by genetic drift. This hypothesis is supported by three arguments: (1) the West-East gradient of prevalence in the haplotype among European populations; (2) ancient DNA from Neolithic burials in the Iberian peninsula, dated 6,600-4,500 years before present, confirmed the relatively high frequency of this haplotype in the region, and (3) no functional differences between this haplotype and wild-type TLR4 have been found. In contrast, the disappearance of the 299Gly/399Thr haplotype in Europe is most likely due to negative selection due to sepsis. In conclusion, differences in distribution of TLR4 polymorphisms Asp299Gly and Thr399Ile in European populations are most likely due to a combination of population migration events combined with selection due to sepsis.
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