rs4986790
| influences a wide variety of both infectious and non-infectious diseases |
| Orientation | plus |
| Stabilized | plus |
| Geno | Mag | Summary |
|---|---|---|
| (A;A) | 0 | normal |
| (A;G) | None | |
| (G;G) | 2.5 | complex; numerous associations reported |
| Reference | GRCh38 38.1/141 |
| Chromosome | 9 |
| Position | 117713024 |
| Gene | TLR4 |
| is a | snp |
| is | mentioned by |
| dbSNP | rs4986790 |
| dbSNP (classic) | rs4986790 |
| ClinGen | rs4986790 |
| ebi | rs4986790 |
| HLI | rs4986790 |
| Exac | rs4986790 |
| Gnomad | rs4986790 |
| Varsome | rs4986790 |
| LitVar | rs4986790 |
| Map | rs4986790 |
| PheGenI | rs4986790 |
| Biobank | rs4986790 |
| 1000 genomes | rs4986790 |
| hgdp | rs4986790 |
| ensembl | rs4986790 |
| geneview | rs4986790 |
| scholar | rs4986790 |
| rs4986790 | |
| pharmgkb | rs4986790 |
| gwascentral | rs4986790 |
| openSNP | rs4986790 |
| 23andMe | rs4986790 |
| SNPshot | rs4986790 |
| SNPdbe | rs4986790 |
| MSV3d | rs4986790 |
| GWAS Ctlg | rs4986790 |
| GMAF | 0.04408 |
| Max Magnitude | 2.5 |
| ? | (A;A) (A;G) (G;G) | 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]
Results of three independent samples did not confirm previously reported association of rs4986790 with AMD, individually or combined.[PMID 19628747
]
[PMID 19267370] Association of IL10 and Other immune response- and obesity-related genes with prostate cancer in CLUE II.
[PMID 19531762] Association Between Toll-like Receptor 4 Gene Polymorphism and Biopsy-proven Giant Cell Arteritis
[PMID 19922963] A functional nonsynonymous toll-like receptor 4 gene polymorphism is associated with metabolic syndrome, surrogates of insulin resistance, and syndromes of lipid accumulation
[PMID 21125016] The D299G/T399I Toll-Like Receptor 4 Variant Associates with Body and Liver Fat: Results from the TULIP and METSIM Studies
[PMID 21306745] 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 21081146] Impact of Toll-like receptor 4 polymorphisms on risk of cancer
[PMID 21837802] Confirmation of an association between single nucleotide polymorphisms in the VDR gene with respiratory syncytial virus related disease in South African Children
[PMID 22348075] Influence of Common Non-Synonymous Toll-like Receptor 4 Polymorphisms on Bronchopulmonary Dysplasia and Prematurity in Human Infants
[PMID 22615793] Investigation of Host Candidate Malaria-Associated Risk/Protective SNPs in a Brazilian Amazonian Population
[PMID 22645142] Variants of Toll-like receptor 4 predict cardiac recovery in patients with dilated cardiomyopathy
[PMID 22662111] Polymorphisms in Toll-Like Receptors 2, 4, and 9 Are Highly Associated with Hearing Loss in Survivors of Bacterial Meningitis
[PMID 22737602] Loss-of-function alleles of P2RX7 and TLR4 fail to affect the response to chemotherapy in non-small cell lung cancer.
| ClinVar | |
|---|---|
| Risk | Rs4986790(G;G) |
| Alt | Rs4986790(G;G) |
| Reference | Rs4986790(A;A) |
| Significance | Non-pathogenic |
| Disease | TLR4 POLYMORPHISM |
| Variation | info |
| Gene | TLR4 |
| CLNDBN | TLR4 POLYMORPHISM |
| Reversed | 0 |
| HGVS | NC_000009.11:g.120475302A>G |
| CLNSRC | OMIM Allelic Variant UniProtKB (protein) |
| CLNACC | RCV000007040.5, |
[PMID 15726497] Gene-environment interaction effects on the development of immune responses in the 1st year of life.
[PMID 16820586] Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.
[PMID 16846490] Lemierre's syndrome and genetic polymorphisms: a case report.
[PMID 16859562] Do host genetic traits in the bacterial sensing system play a role in the development of Chlamydia trachomatis-associated tubal pathology in subfertile women?
[PMID 16954131] Toll-like receptor 4 gene polymorphisms and myocardial infarction: no association in a Caucasian population.
[PMID 17062130] Polymorphisms within inflammatory genes and colorectal cancer.
[PMID 17327408] Prognostic significance of host immune gene polymorphisms in follicular lymphoma survival.
[PMID 17592300] Genetic polymorphisms and the risk of infection following esophagectomy. positive association with TNF-alpha gene -308 genotype.
[PMID 17668374] Combining evidence of natural selection with association analysis increases power to detect malaria-resistance variants.
[PMID 17699831] Toll-like receptor 4 polymorphism associated with the response to whole-cell pertussis vaccination in children from the KOALA study.
[PMID 17708757] Genome bioinformatic analysis of nonsynonymous SNPs.
[PMID 17827388] Genetic variation in 1253 immune and inflammation genes and risk of non-Hodgkin lymphoma.
[PMID 18062835] Novel insight in the association between salmonellosis or campylobacteriosis and chronic illness, and the role of host genetics in susceptibility to these diseases.
[PMID 18172114] Comprehensive analysis of the candidate genes CCL2, CCR2, and TLR4 in age-related macular degeneration.
[PMID 18298826] Association between variations in the TLR4 gene and incident type 2 diabetes is modified by the ratio of total cholesterol to HDL-cholesterol.
[PMID 18307517] Common studied polymorphisms do not affect plasma cytokine levels upon endotoxin exposure in humans.
[PMID 18325643] Associations between SNPs in toll-like receptors and related intracellular signaling molecules and immune responses to measles vaccine: preliminary results.
[PMID 18382655] Maternal TLR4 and NOD2 gene variants, pro-inflammatory phenotype and susceptibility to early-onset preeclampsia and HELLP syndrome.
[PMID 18396467] Genetic variation and haplotype structures of innate immunity genes in eastern India.
[PMID 18422738] Study of Toll-like receptor gene loci in sarcoidosis.
[PMID 18549840] 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.
[PMID 18633131] 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.
[PMID 18635889] Toll-like receptor 1 polymorphisms affect innate immune responses and outcomes in sepsis.
[PMID 18753640] Toll-like receptor 3 and geographic atrophy in age-related macular degeneration.
[PMID 18936436] Prevalence in the United States of selected candidate gene variants: Third National Health and Nutrition Examination Survey, 1991-1994.
[PMID 18975326] Toll-like receptor 2 variants are associated with acute reactive arthritis.
[PMID 19029192] A pooled investigation of Toll-like receptor gene variants and risk of non-Hodgkin lymphoma.
[PMID 19066394] Organochlorine exposure, immune gene variation, and risk of non-Hodgkin lymphoma.
[PMID 19131814] Variation in the TLR4 gene influences the risk of organ failure and shock posttrauma: a cohort study.
[PMID 19134200] No evidence of major effects in several Toll-like receptor gene polymorphisms in rheumatoid arthritis.
[PMID 19277200] Toll-like receptor 4 (TLR4) and typhoid fever in Vietnam.
[PMID 19337058] CD14-159C/T and TLR9-1237T/C polymorphisms are not associated with gastric cancer risk in Caucasian populations.
[PMID 19505919] Toll-like receptor signaling pathway variants and prostate cancer mortality.
[PMID 19543401] Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women.
[PMID 19586676] Multiple variants in toll-like receptor 4 gene modulate risk of liver fibrosis in Caucasians with chronic hepatitis C infection.
[PMID 20011079] Lack of association between toll-like receptor 4 gene polymorphisms and sarcoidosis-related uveitis in Japan.
[PMID 20016852] Genetic variation of the human urinary tract innate immune response and asymptomatic bacteriuria in women.
[PMID 20026892] [Association of Toll-like receptor gene with Crohn's disease in Koreans].
[PMID 20200442] Sequence variants in the TLR4 and TLR6-1-10 genes and prostate cancer risk. Results based on pooled analysis from three independent studies.
[PMID 20525286] 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.
[PMID 20646321] Toll-like receptor (TLR) and nucleosome-binding oligomerization domain (NOD) gene polymorphisms and endometrial cancer risk.
[PMID 20671584] Toll-like receptor 4 gene polymorphisms show no association with the risk of clinical or angiographic restenosis after percutaneous coronary intervention.
[PMID 20818961] Inflammatory mediators gene polymorphisms in preeclampsia.
[PMID 21214494] Molecular pathogenesis of endometriosis; Toll-like receptor-4 A896G (D299G) polymorphism: a novel explanation.
[PMID 21385363] Polymorphisms in genes controlling inflammation and tissue repair in rheumatoid arthritis: a case control study.
[PMID 22300618] Toll-like 4 receptor variant, Asp299Gly, and reduced risk of hemorrhagic cystitis after hematopoietic stem cell transplantation.
[PMID 22360682] Lack of Association Between TLR4 rs4986790 Polymorphism and Risk of Cardiovascular Disease in Patients with Rheumatoid Arthritis.
[PMID 23084080] The TLR4 gene polymorphisms and susceptibility to cancer: A systematic review and meta-analysis
[PMID 23093310] Toll Like Receptor 4 D299G Associates with Disease Progression in Caucasian Patients with Chronic HBV Infection: Relationship with Gender
[PMID 22691414] 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
[PMID 22494793] Innate immunity gene single nucleotide polymorphisms and otitis media
[PMID 23151015] Toll-like receptor 3 gene polymorphisms and severity of pandemic A/H1N1/2009 influenza in otherwise healthy children
[PMID 23179660] Prospective study of effect modification by Toll-like receptor 4 variation on the association between Trichomonas vaginalis serostatus and prostate cancer
[PMID 22809755] Immune defense single nucleotide polymorphisms and recruitment strategies associated with contact lens keratitis
[PMID 23420357] Meta-analysis demonstrates association between TLR polymorphisms and rheumatoid arthritis
[PMID 23086128] Profiles of gene polymorphisms in cytokines and Toll-like receptors with higher risk for gastric cancer
[PMID 23021866] Toll-like receptor gene variants associated with bacterial vaginosis among HIV-1 infected adolescents
[PMID 23349936] Determinants of serum concentrations of lipopolysaccharide-binding protein (LBP) in the adult population: the role of obesity
[PMID 23867959] Toll-like receptor genetic variants are associated with Gram-negative infections in VLBW infants
[PMID 24028589] TLR2, TLR3, TLR4 and CD14 gene polymorphisms associated with oral lichen planus risk
[PMID 24447403] TLR4 polymorphism is not associated with biopsy proven giant cell arteritis
[PMID 22573572] Phenotype-genotype profiles in Crohn's disease predicted by genetic markers in autophagy-related genes (GOIA study II).
[PMID 22740716] Toll-like receptor and hepatitis B virus clearance in chronic infected patients: a long-term prospective cohort study in Taiwan.
[PMID 23161283] SNPs in toll-like receptor (TLR) genes as new genetic alterations associated with congenital toxoplasmosis?
[PMID 23289617] Genetic variation of TLR2 and TLR4 among the Saudi Arabian population: insight into the evolutionary dynamics of the Arabian Peninsula.
[PMID 23417289] Coding variants of TLR2 and TLR4 genes do not substantially contribute to prosthetic joint infection.
[PMID 23447684] Impaired TLR5 functionality is associated with survival in melioidosis.
[PMID 23455702] TLR4, IL10RA, and NOD2 mutation in paediatric Crohn's disease patients: an association with Mycobacterium avium subspecies paratuberculosis and TLR4 and IL10RA expression.
[PMID 23459936] Exploring the genetic basis of chronic periodontitis: a genome-wide association study.
[PMID 24803744] Evidences of +896 A/G TLR4 Polymorphism as an Indicative of Prevalence of Complications in T2DM Patients
[PMID 25177689] The Association of Toll-Like Receptor 4 Polymorphism with Hepatitis C Virus Infection in Saudi Arabian Patients
[PMID 25213166] An association between single nucleotide polymorphisms within TLR and TREM-1 genes and infective endocarditis
[PMID 24349054] No correlation between PNPLA3 rs738409 genotype and fatty liver and hepatic cirrhosis in Japanese patients with HCV
[PMID 25675790] [Incidence of odontogenic phlegmon, associated with polymorph variant 896A/G of gene TLR4, but not 2258G/A of gene TLR2]
[PMID 18275280] Polymorphisms in Toll-Like Receptor Genes and Susceptibility to Pulmonary Aspergillosis
[PMID 26015800] Association of Toll-like receptor 4 polymorphism with age-dependent systolic blood pressure increase in patients with coronary artery disease
[PMID 25360682] Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis
[PMID 26174031] TLR4 Asp299Gly polymorphism may be protective against chronic periodontitis
[PMID 25422198] Polymorphic variation of inflammation-related genes and risk of non-Hodgkin lymphoma for Uygur and Han Chinese in Xinjiang
[PMID 26435700] Obesity-associated hypertension is ameliorated in patients with TLR4 single nucleotide polymorphism (SNP) rs4986790
[PMID 26846412] Ancestry informative markers and selected single nucleotide polymorphisms in immunoregulatory genes on preterm labor and preterm premature rupture of membranes: a case control study.
[PMID 26919710] Variations in genes involved in regulation of the nuclear factor - κB pathway and the risk of acute myeloid leukaemia.
[PMID 25542762] Poststroke fatigue: hints to a biological mechanism.
[PMID 27155792] TLR2 and TLR4 polymorphisms in Southern Chinese Psoriasis Vulgaris patients.
[PMID 28241976] Influence of toll-like receptor 4 gene variants and plasma fatty acid profile on systemic inflammation: A population-based cross-sectional study.
[PMID 28510725] IFITM3, TLR3, and CD55 Genes SNPs and Cumulative Ge-netic Risks for Severe Outcomes in Chinese Patients with H7N9 / H1N1pdm09 Influenza.
[PMID 30131040] [Fibrogenesis Genes and Susceptibility to Coronary Atherosclerosis].
[PMID 30421643] TLR3 and TLR4 SNP variants in the liver disease resulting from hepatitis B virus and hepatitis C virus infection.
[PMID 30529560] Genetic variation in TLR pathway and the risk of pulmonary tuberculosis in a Moldavian population.
[PMID 31749314] Association of Toll-like 4 receptor gene polymorphism (rs4986790, rs4986791) with the risk of urinary tract infection: A systematic review and meta-analysis.
[PMID 31755594] Toll-like receptor 4 polymorphisms were associated with low serum pro-inflammatory cytokines in BCG osteitis survivors.
[PMID 31772831] TLR4 polymorphisms may increase susceptibility to periodontitis in Pg-positive individuals.
[PMID 31996057] Study of Toll‑Like Receptor 4 Gene Polymorphisms in Colorectal Cancer: Correlation with Clinicopathological Features.
[PMID 32753695] TLR4 896A/G and TLR9 1174G/A polymorphisms are associated with the risk of infectious mononucleosis.
[PMID 33396586] Strong Association of the rs4986790 Single Nucleotide Polymorphism (SNP) of the Toll-Like Receptor 4 (TLR4) Gene with Human Immunodeficiency Virus (HIV) Infection: A Meta-Analysis.
