{{Rsnum
|rsid=4986790
|Gene=TLR4
|Chromosome=9
|position=117713024
|Orientation=plus
|ReferenceAllele=A
|MissenseAllele=G
|GMAF=0.04408
|Assembly=GRCh38
|GenomeBuild=38.1
|dbSNPBuild=141
|Summary=influences a wide variety of both infectious and non-infectious diseases
|geno1=(A;A)
|geno2=(A;G)
|geno3=(G;G)
|Gene_s=TLR4
}}{{ population diversity
| geno1=(A;A)
| geno2=(A;G)
| geno3=(G;G)
| CEU | 93.8 | 5.3 | 0.9
| HCB | 100.0 | 0.0 | 0.0
| JPT | 100.0 | 0.0 | 0.0
| YRI | 91.8 | 8.2 | 0.0
| ASW | 91.2 | 7.0 | 1.8
| CHB | 100.0 | 0.0 | 0.0
| CHD | 0.0 | 0.0 | 0.0
| GIH | 82.0 | 17.0 | 1.0
| LWK | 81.3 | 18.7 | 0.0
| MEX | 93.0 | 7.0 | 0.0
| MKK | 85.1 | 14.3 | 0.6
| TSI | 91.2 | 8.8 | 0.0
| HapMapRevision=28
}}[[rs4986790]], a SNP also known as Asp299Gly (and also 896A/G) in the [[TLR4]] gene, is often studied along with a cosegregating SNP known as Thr399Ile, [[rs4986791]]. ([[TLR4]] encodes a receptor involved in the innate immune response.) Together, these SNPs have been reported to be associated with a wide variety of both infectious and non-infectious diseases, although there are conflicting or even contradictory results also reported in some cases. The risk allele for [[rs4986790]] is (G).

Reported associations include {{PMID|15766650}}:

* [[Diabetic neuropathy]]
** These SNPs may be protective {{PMID|14693986}}

* [[Heart disease]]
** Men with the risk alleles for both SNPs are at increased risk for myocardial infarction in this study of over 2000 individuals. {{PMID|15576653}}
** [[rs4986790]](G) carriers are not at increased risk for myocardial infartions, at least in this study of ~200 individuals. {{PMID|15547160}}
** [[rs4986790]](G) carriers are less likely to have heart attacks, in this study of ~400 individuals. {{PMID|14563652}}
** Individuals with the risk alleles for both SNPs have a lower incidence of carotid stenosis {{PMID|12124407}}

* [[Premature birth]]
** Individuals with the risk alleles for both SNPs have a higher incidence for having their pregnancies associated with [[premature birth]] {{PMID|12193670}}

* [[Bacterial vaginosis]]
** Pregnant [[rs4986790]](G) carriers are at increased risk for higher pH and a 10 fold higher level of certain bacteria {{PMID|15358455}}

* [[Bacterial infection]]
** Individuals with the risk alleles for both SNPs are more prone to gram-negative bacterial infections {{PMID|12404174}}

* [[Septic shock]]
** Individuals with the risk alleles for both SNPs are at higher risk for [[septic shock]] {{PMID|11996613}}

* [[Respiratory syncytial virus infection]]
** Individuals with the risk alleles for both SNPs are at higher risk for this type of viral infection. {{PMID|15143473}}

* [[Asthma]]
** Although not seen to influence the incidence of developing [[asthma]], [[rs4986790]](G) carriers who had [[asthma]] are reported to be more severely affected. {{PMID|14735148}}

* [[Allograft rejection]]
** Carriers of the risk alleles of either [[rs4986790]] or [[rs4986791]] have a lower rate of acute [[allograft rejection]] following lung transplantation. {{PMID|12773319}}

* [[Alzheimer's disease]]
** A study of 626 Northern Italian Alzheimer patients (427 women and 199 men; age range: 53-98 years; mean age: 74.88 +/- 8.44) found that [[rs4986790]] was associated with increased risk for the disease.{{PMID|18991680}}{{PMID|19006850}}

* [[cirrhosis]] [[rs4986790]] and [[rs4986791]] {{PMID|19085953|OA=1
}}

Results of three independent samples did not confirm previously reported association of [[rs4986790]] with AMD, individually or combined.{{PMID|19628747|OA=1
}}

{{omim
|desc=ENDOTOXIN HYPORESPONSIVENESS
|id=603030
|quiet=1
|rsnum=4986790
|variant=0001
}}

{{ neighbor
| rsid = 4986791
| distance = 300
}}

{{PMID Auto
|PMID=19267370
|Title=Association of IL10 and Other immune response- and obesity-related genes with prostate cancer in CLUE II.
|OA=1
}}

{{PMID Auto
|PMID=19531762
|Title=Association Between Toll-like Receptor 4 Gene Polymorphism and Biopsy-proven Giant Cell Arteritis
}}

{{PMID Auto
|PMID=19922963
|Title=A functional nonsynonymous toll-like receptor 4 gene polymorphism is associated with metabolic syndrome, surrogates of insulin resistance, and syndromes of lipid accumulation
}}

{{PharmGKB
|RSID=rs4986790
|Name_s=TLR4: D299G
|Gene_s=TLR4
|Feature=
|Evidence=PubMed ID:18946062
|Annotation=A study in 336 recipients of hematopoietic-cell transplants and their unrelated donors suggests an association between the donor TLR4 haplotype S4 (this SNP and SNP T399I in a strong linkage disequilibrium) and the risk of invasive aspergillosis among recipients of hematopoietic-cell transplants from unrelated donors.
|Drugs=
|Drug Classes=
|Diseases=Aspergillosis Infection
|Curation Level=Curated
|PharmGKB Accession ID=PA162356100
}}

{{PMID Auto
|PMID=21125016
|Title=The D299G/T399I Toll-Like Receptor 4 Variant Associates with Body and Liver Fat: Results from the TULIP and METSIM Studies
|OA=1
}}

{{PMID Auto
|PMID=21306745
|Title=Polymorphisms in Toll-like receptor 4 are associated with factors of the metabolic syndrome and modify the association between dietary saturated fat and fasting high-density lipoprotein cholesterol
}}

{{PMID Auto
|PMID=21081146
|Title=Impact of Toll-like receptor 4 polymorphisms on risk of cancer
}}

{{PMID Auto
|PMID=21837802
|Title=Confirmation of an association between single nucleotide polymorphisms in the VDR gene with respiratory syncytial virus related disease in South African Children
}}

{{PMID Auto
|PMID=22348075
|Title=Influence of Common Non-Synonymous Toll-like Receptor 4 Polymorphisms on Bronchopulmonary Dysplasia and Prematurity in Human Infants
|OA=1
}}

{{PMID Auto
|PMID=22615793
|Title=Investigation of Host Candidate Malaria-Associated Risk/Protective SNPs in a Brazilian Amazonian Population
|OA=1
}}

{{PMID Auto
|PMID=22645142
|Title=Variants of Toll-like receptor 4 predict cardiac recovery in patients with dilated cardiomyopathy
|OA=1
}}

{{PMID Auto
|PMID=22662111
|Title=Polymorphisms in Toll-Like Receptors 2, 4, and 9 Are Highly Associated with Hearing Loss in Survivors of Bacterial Meningitis
|OA=1
}}

{{PMID Auto
|PMID=22737602
|Title=Loss-of-function alleles of P2RX7 and TLR4 fail to affect the response to chemotherapy in non-small cell lung cancer.
|OA=1
}}

{{ClinVar
|rsid=4986790
|Reversed=0
|FwdREF=A
|FwdALT=G
|REF=A
|ALT=G
|RSPOS=120475302
|CHROM=9
|GMAF=0.0444
|dbSNPBuildID=113
|SSR=0
|SAO=1
|VP=0x050368000000150517110100
|GENEINFO=TLR4:7099
|GENE_NAME=TLR4
|GENE_ID=7099
|WGT=0
|VC=SNV
|CLNALLE=1
|CLNHGVS=NC_000009.11:g.120475302A>G
|CLNORIGIN=1
|CLNSIG=255
|Tags=PM;PMC;S3D;SLO;VLD;G5;HD;GNO;KGPhase1;KGPROD;OTHERKG;PH3;LSD;OM
|CAF=0.9559; 0.04408
|CLNACC=RCV000007040.1; RCV000007041.1; RCV000007042.1
|CLNDBN=Endotoxin hyporesponsiveness; MACULAR DEGENERATION, AGE-RELATED, 10, SUSCEPTIBILITY TO; Colorectal cancer, susceptibility to
|CLNDSDB=MedGen
|CLNDSDBID=C1864267
|CLNSRC=OMIM Allelic Variant
|CLNSRCID=603030.0001
|COMMON=1
|Disease=Endotoxin hyporesponsiveness; MACULAR DEGENERATION; Colorectal cancer
}}

{{PMID Auto
|PMID=15726497
|Title=Gene-environment interaction effects on the development of immune responses in the 1st year of life.
|OA=1
}}

{{PMID Auto
|PMID=16820586
|Title=Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.
|OA=1
}}

{{PMID Auto
|PMID=16846490
|Title=Lemierre's syndrome and genetic polymorphisms: a case report.
|OA=1
}}

{{PMID Auto
|PMID=16859562
|Title=Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women?
|OA=1
}}

{{PMID Auto
|PMID=16954131
|Title=Toll-like receptor 4 gene polymorphisms and myocardial infarction: no association in a Caucasian population.
}}

{{PMID Auto
|PMID=17062130
|Title=Polymorphisms within inflammatory genes and colorectal cancer.
|OA=1
}}

{{PMID Auto
|PMID=17327408
|Title=Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival.
|OA=1
}}

{{PMID Auto
|PMID=17592300
|Title=Genetic polymorphisms and the risk of infection following esophagectomy. positive association with TNF-alpha gene -308 genotype.
|OA=1
}}

{{PMID Auto
|PMID=17668374
|Title=Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants.
|OA=1
}}

{{PMID Auto
|PMID=17699831
|Title=Toll-like receptor 4 polymorphism associated with the response to whole-cell pertussis vaccination in children from the KOALA study.
|OA=1
}}

{{PMID Auto
|PMID=17708757
|Title=Genome bioinformatic analysis of nonsynonymous SNPs.
|OA=1
}}

{{PMID Auto
|PMID=17827388
|Title=Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma.
|OA=1
}}

{{PMID Auto
|PMID=18062835
|Title=Novel insight in the association between salmonellosis or campylobacteriosis and chronic illness, and the role of host genetics in susceptibility to these diseases.
|OA=1
}}

{{PMID Auto
|PMID=18172114
|Title=Comprehensive analysis of the candidate genes CCL2, CCR2, and TLR4 in age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=18298826
|Title=Association between variations in the TLR4 gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol.
|OA=1
}}

{{PMID Auto
|PMID=18307517
|Title=Common studied polymorphisms do not affect plasma cytokine levels upon endotoxin exposure in humans.
|OA=1
}}

{{PMID Auto
|PMID=18325643
|Title=Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results.
|OA=1
}}

{{PMID Auto
|PMID=18382655
|Title=Maternal TLR4 and NOD2 gene variants, pro-inflammatory phenotype and susceptibility to early-onset preeclampsia and HELLP syndrome.
|OA=1
}}

{{PMID Auto
|PMID=18396467
|Title=Genetic variation and haplotype structures of innate immunity genes in eastern India.
|OA=1
}}

{{PMID Auto
|PMID=18422738
|Title=Study of Toll-like receptor gene loci in sarcoidosis.
|OA=1
}}

{{PMID Auto
|PMID=18549840
|Title=Cholesterol ester transfer protein, interleukin-8, peroxisome proliferator activator receptor alpha, and Toll-like receptor 4 genetic variations and risk of incident nonfatal myocardial infarction and ischemic stroke.
|OA=1
}}

{{PMID Auto
|PMID=18633131
|Title=Host immune gene polymorphisms in combination with clinical and demographic factors predict late survival in diffuse large B-cell lymphoma patients in the pre-rituximab era.
|OA=1
}}

{{PMID Auto
|PMID=18635889
|Title=Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis.
|OA=1
}}

{{PMID Auto
|PMID=18753640
|Title=Toll-like receptor 3 and geographic atrophy in age-related macular degeneration.
|OA=1
}}

{{PMID Auto
|PMID=18936436
|Title=Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
|OA=1
}}

{{PMID Auto
|PMID=18975326
|Title=Toll-like receptor 2 variants are associated with acute reactive arthritis.
}}

{{PMID Auto
|PMID=19029192
|Title=A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma.
|OA=1
}}

{{PMID Auto
|PMID=19066394
|Title=Organochlorine exposure, immune gene variation, and risk of non-Hodgkin lymphoma.
|OA=1
}}

{{PMID Auto
|PMID=19131814
|Title=Variation in the TLR4 gene influences the risk of organ failure and shock posttrauma: a cohort study.
|OA=1
}}

{{PMID Auto
|PMID=19134200
|Title=No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoid arthritis.
|OA=1
}}

{{PMID Auto
|PMID=19277200
|Title=Toll-like receptor 4 (TLR4) and typhoid fever in Vietnam.
|OA=1
}}

{{PMID Auto
|PMID=19337058
|Title=CD14-159C/T and TLR9-1237T/C polymorphisms are not associated with gastric cancer risk in Caucasian populations.
|OA=1
}}

{{PMID Auto
|PMID=19505919
|Title=Toll-like receptor signaling pathway variants and prostate cancer mortality.
|OA=1
}}

{{PMID Auto
|PMID=19543401
|Title=Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women.
|OA=1
}}

{{PMID Auto
|PMID=19586676
|Title=Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in Caucasians with chronic hepatitis C infection.
|OA=1
}}

{{PMID Auto
|PMID=20011079
|Title=Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan.
|OA=1
}}

{{PMID Auto
|PMID=20016852
|Title=Genetic variation of the human urinary tract innate immune response and asymptomatic bacteriuria in women.
|OA=1
}}

{{PMID Auto
|PMID=20026892
|Title=[Association of Toll-like receptor gene with Crohn's disease in Koreans].
}}

{{PMID Auto
|PMID=20200442
|Title=Sequence variants in the TLR4 and TLR6-1-10 genes and prostate cancer risk. Results based on pooled analysis from three independent studies.
|OA=1
}}

{{PMID Auto
|PMID=20525286
|Title=Influence of genetic variations in TLR4 and TIRAP/Mal on the course of sepsis and pneumonia and cytokine release: an observational study in three cohorts.
|OA=1
}}

{{PMID Auto
|PMID=20646321
|Title=Toll-like receptor (TLR) and nucleosome-binding oligomerization domain (NOD) gene polymorphisms and endometrial cancer risk.
|OA=1
}}

{{PMID Auto
|PMID=20671584
|Title=Toll-like receptor 4 gene polymorphisms show no association with the risk of clinical or angiographic restenosis after percutaneous coronary intervention.
}}

{{PMID Auto
|PMID=20818961
|Title=Inflammatory mediators gene polymorphisms in preeclampsia.
}}

{{PMID Auto
|PMID=21214494
|Title=Molecular pathogenesis of endometriosis; Toll-like receptor-4 A896G (D299G) polymorphism: a novel explanation.
}}

{{PMID Auto
|PMID=21385363
|Title=Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study.
|OA=1
}}

{{PMID Auto
|PMID=22300618
|Title=Toll-like 4 receptor variant, Asp299Gly, and reduced risk of hemorrhagic cystitis after hematopoietic stem cell transplantation.
}}

{{PMID Auto
|PMID=22360682
|Title=Lack of Association Between TLR4 rs4986790 Polymorphism and Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis.
|OA=1
}}

{{GET Evidence
|gene=TLR4
|aa_change=Asp299Gly
|aa_change_short=D299G
|impact=pathogenic
|qualified_impact=Insufficiently evaluated pathogenic
|inheritance=unknown
|quality_scores=Array
|dbsnp_id=rs4986790
|overall_frequency_n=700
|overall_frequency_d=10758
|overall_frequency=0.0650679
|n_genomes=4
|n_genomes_annotated=0
|n_haplomes=4
|n_articles=0
|n_articles_annotated=0
|in_omim=Y
|pph2_score=0.006
|nblosum100=4
|autoscore=2
|webscore=N
}}

{{PMID Auto
|PMID=23084080
|Title=The TLR4 gene polymorphisms and susceptibility to cancer: A systematic review and meta-analysis
}}

{{PMID Auto
|PMID=23093310
|Title=Toll Like Receptor 4 D299G Associates with Disease Progression in Caucasian Patients with Chronic HBV Infection: Relationship with Gender
}}

{{PMID Auto
|PMID=22691414
|Title=Role of polymorphisms of toll-like receptor (TLR) 4, TLR9, toll-interleukin 1 receptor domain containing adaptor protein (TIRAP) and FCGR2A genes in malaria susceptibility and severity in Burundian children
|OA=1
}}

{{PMID Auto
|PMID=22494793
|Title=Innate immunity gene single nucleotide polymorphisms and otitis media
}}

{{PMID Auto
|PMID=23151015
|Title=Toll-like receptor 3 gene polymorphisms and severity of pandemic A/H1N1/2009 influenza in otherwise healthy children
|OA=1
}}

{{PMID Auto
|PMID=23179660
|Title=Prospective study of effect modification by Toll-like receptor 4 variation on the association between Trichomonas vaginalis serostatus and prostate cancer
|OA=1
}}

{{PMID Auto
|PMID=22809755
|Title=Immune defense single nucleotide polymorphisms and recruitment strategies associated with contact lens keratitis
}}

{{PMID Auto
|PMID=23420357
|Title=Meta-analysis demonstrates  association  between TLR polymorphisms and  rheumatoid arthritis
}}

{{PMID Auto
|PMID=23086128
|Title=Profiles of gene polymorphisms in cytokines and Toll-like receptors with higher risk for gastric cancer
}}

{{PMID Auto
|PMID=23021866
|Title=Toll-like receptor gene variants associated with bacterial vaginosis among HIV-1 infected adolescents
|OA=1
}}

{{PMID Auto
|PMID=23349936
|Title=Determinants of serum concentrations of lipopolysaccharide-binding protein (LBP) in the adult population: the role of obesity
|OA=1
}}

{{PMID Auto
|PMID=23867959
|Title=Toll-like receptor genetic variants are associated with Gram-negative infections in VLBW infants
}}

{{PMID Auto
|PMID=24028589
|Title=TLR2, TLR3, TLR4 and CD14 gene polymorphisms associated with oral lichen planus risk
}}

{{PMID Auto
|PMID=24447403
|Title=TLR4 polymorphism is not associated with biopsy proven giant cell arteritis
}}

{{PMID Auto
|PMID=22573572
|Title=Phenotype-genotype profiles in Crohn's disease predicted by genetic markers in autophagy-related genes (GOIA study II).
}}

{{PMID Auto
|PMID=22740716
|Title=Toll-like receptor and hepatitis B virus clearance in chronic infected patients: a long-term prospective cohort study in Taiwan.
}}

{{PMID Auto
|PMID=23161283
|Title=SNPs in toll-like receptor (TLR) genes as new genetic alterations associated with congenital toxoplasmosis?
|OA=1
}}

{{PMID Auto
|PMID=23289617
|Title=Genetic variation of TLR2 and TLR4 among the Saudi Arabian population: insight into the evolutionary dynamics of the Arabian Peninsula.
}}

{{PMID Auto
|PMID=23417289
|Title=Coding variants of TLR2 and TLR4 genes do not substantially contribute to prosthetic joint infection.
}}

{{PMID Auto
|PMID=23447684
|Title=Impaired TLR5 functionality is associated with survival in melioidosis.
|OA=1
}}

{{PMID Auto
|PMID=23455702
|Title=TLR4, IL10RA, and NOD2 mutation in paediatric Crohn's disease patients: an association with Mycobacterium avium subspecies paratuberculosis and TLR4 and IL10RA expression.
}}

{{PMID Auto
|PMID=23459936
|Title=Exploring the genetic basis of chronic periodontitis: a genome-wide association study.
|OA=1
}}

{{PMID Auto
|PMID=24803744
|Title=Evidences of +896 A/G TLR4 Polymorphism as an Indicative of Prevalence of Complications in T2DM Patients
|OA=1
}}

{{PMID Auto
|PMID=25177689
|Title=The Association of Toll-Like Receptor 4 Polymorphism with Hepatitis C Virus Infection in Saudi Arabian Patients
}}

{{PMID Auto
|PMID=25213166
|Title=An association between single nucleotide polymorphisms within TLR and TREM-1 genes and infective endocarditis
}}

{{PMID Auto
|PMID=24349054
|Title=No correlation between PNPLA3 rs738409 genotype and fatty liver and hepatic cirrhosis in Japanese patients with HCV
}}
{{on chip | 23andMe v1}}
{{on chip | 23andMe v2}}
{{on chip | 23andMe v3}}
{{on chip | 23andMe v4}}
{{on chip | FTDNA2}}
{{on chip | FTDNA}}
{{on chip | Illumina Human 1M}}