rs4986791
| Orientation | plus |
| Stabilized | plus |
| Geno | Mag | Summary |
|---|---|---|
| (C;C) | 0 | normal |
| (C;T) | complex; see details | |
| (T;T) | 2.5 | complex; see details |
| Reference | GRCh38 38.1/141 |
| Chromosome | 9 |
| Position | 117713324 |
| Gene | TLR4 |
| is a | snp |
| is | mentioned by |
| dbSNP | rs4986791 |
| dbSNP (classic) | rs4986791 |
| ClinGen | rs4986791 |
| ebi | rs4986791 |
| HLI | rs4986791 |
| Exac | rs4986791 |
| Gnomad | rs4986791 |
| Varsome | rs4986791 |
| LitVar | rs4986791 |
| Map | rs4986791 |
| PheGenI | rs4986791 |
| Biobank | rs4986791 |
| 1000 genomes | rs4986791 |
| hgdp | rs4986791 |
| ensembl | rs4986791 |
| geneview | rs4986791 |
| scholar | rs4986791 |
| rs4986791 | |
| pharmgkb | rs4986791 |
| gwascentral | rs4986791 |
| openSNP | rs4986791 |
| 23andMe | rs4986791 |
| SNPshot | rs4986791 |
| SNPdbe | rs4986791 |
| MSV3d | rs4986791 |
| GWAS Ctlg | rs4986791 |
| GMAF | 0.02984 |
| Max Magnitude | 2.5 |
| ? | (C;C) (C;T) (T;T) | 28 |
|---|---|---|
|
| ||
rs4986791, a SNP also known as Thr399Ile (and also 1196C/T) in the TLR4 gene, is often studied along with a cosegregating SNP known as Asp299Gly, rs4986790. (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 rs4986791 is (T).
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 are at higher risk 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]
- Allograft complications
- A study of 300+ recipients of hematopoietic-cell transplants concluded that the adjusted hazard ratio for a recipient of developing a life-threatening invasive aspergillosis infection was 6.16x higher (CI: 1.97-19.26, p=0.002) if the donor carried these TLR4 risk alleles. This risk was statistically significant for unrelated recipients of transplants (odds ratio, 5.0, CI: 1.04-24.01, p=0.04) but did not quite meet the p=0.05 significance criteria for related recipients (odds ratio, 2.29, CI: 0.93-5.68, p=0.07). [PMID 18946062
]
- A study of 300+ recipients of hematopoietic-cell transplants concluded that the adjusted hazard ratio for a recipient of developing a life-threatening invasive aspergillosis infection was 6.16x higher (CI: 1.97-19.26, p=0.002) if the donor carried these TLR4 risk alleles. This risk was statistically significant for unrelated recipients of transplants (odds ratio, 5.0, CI: 1.04-24.01, p=0.04) but did not quite meet the p=0.05 significance criteria for related recipients (odds ratio, 2.29, CI: 0.93-5.68, p=0.07). [PMID 18946062
[PMID 21283657
] Gallbladder Cancer Predisposition: A Multigenic Approach to DNA-Repair, Apoptotic and Inflammatory Pathway Genes
[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 22286521] Polymorphism of the TLR4 Gene Reduces the Risk of Hepatitis C Virus-Induced Hepatocellular Carcinoma
[PMID 22645142] Variants of Toll-like receptor 4 predict cardiac recovery in patients with dilated cardiomyopathy
| ClinVar | |
|---|---|
| Risk | Rs4986791(T;T) |
| Alt | Rs4986791(T;T) |
| Reference | Rs4986791(C;C) |
| Significance | Non-pathogenic |
| Disease | TLR4 POLYMORPHISM not provided |
| Variation | info |
| Gene | TLR4 |
| CLNDBN | TLR4 POLYMORPHISM not provided |
| Reversed | 0 |
| HGVS | NC_000009.11:g.120475602C>T |
| CLNSRC | OMIM Allelic Variant UniProtKB (protein) |
| CLNACC | RCV000007043.4, RCV000086999.1, |
[PMID 16820586] Inflammatory gene polymorphisms and risk of postoperative myocardial infarction after cardiac surgery.
[PMID 16954131] Toll-like receptor 4 gene polymorphisms and myocardial infarction: no association in a Caucasian population.
[PMID 17667860] Toll-like receptor 2 polymorphism is associated with preterm birth.
[PMID 17699831] Toll-like receptor 4 polymorphism associated with the response to whole-cell pertussis vaccination in children from the KOALA study.
[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 18753640] Toll-like receptor 3 and geographic atrophy in age-related macular degeneration.
[PMID 18975326] Toll-like receptor 2 variants are associated with acute reactive arthritis.
[PMID 18987746] Association of interacting genes in the toll-like receptor signaling pathway and the antibody response to pertussis vaccination.
[PMID 19085953] Functional linkage of cirrhosis-predictive single nucleotide polymorphisms of Toll-like receptor 4 to hepatic stellate cell responses.
[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 19543401] Toll-like receptor polymorphisms and susceptibility to urinary tract infections in adult women.
[PMID 19567509] Genetic variants and prostate cancer risk: candidate replication and exploration of viral restriction genes.
[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 20463618] Role of polymorphic variants as genetic modulators of infection in neonatal sepsis.
[PMID 20492496] Significant association between toll-like receptor gene polymorphisms and gallbladder cancer.
[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 20671584] Toll-like receptor 4 gene polymorphisms show no association with the risk of clinical or angiographic restenosis after percutaneous coronary intervention.
[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 22348075] Influence of common non-synonymous Toll-like receptor 4 polymorphisms on bronchopulmonary dysplasia and prematurity in human infants.
[PMID 23084080] The TLR4 gene polymorphisms and susceptibility to cancer: A systematic review and meta-analysis
[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 23086128] Profiles of gene polymorphisms in cytokines and Toll-like receptors with higher risk for gastric cancer
[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 23071570] Gene-gene interaction and functional impact of polymorphisms on innate immune genes in controlling Plasmodium falciparum blood infection level.
[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 23459936] Exploring the genetic basis of chronic periodontitis: a genome-wide association study.
[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 25360682] Polymorphisms of an innate immune gene, toll-like receptor 4, and aggressive prostate cancer risk: a systematic review and meta-analysis
[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 27069792] Association of NOD1, CXCL16, STAT6 and TLR4 gene polymorphisms with Malaysian patients with Crohn's disease
[PMID 27155792] TLR2 and TLR4 polymorphisms in Southern Chinese Psoriasis Vulgaris patients.
[PMID 27526043] Lack of Association Between Polymorphism rs4986791 in TLR4 and Primary Open-Angle Glaucoma in a Saudi Cohort.
[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 30423580] Biochemical Markers, Genotype, and Inflammation in Pediatric Inflammatory Bowel Disease: A Danish Population-Based Study.
[PMID 30594449] Interaction between toll-like receptor 4 (TLR4) gene and alcohol drinking on Parkinson's disease risk in Chinese Han population.
[PMID 31697008] Association of single-nucleotide polymorphisms in TLR4 gene and gene- environment interaction with primary open angle glaucoma in a Chinese northern 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 32349318] TLR4 T399I Polymorphism and Endometriosis in a Cohort of Italian Women.
[PMID 32421725] Association between single nucleotide polymorphisms (SNPs) of IL1, IL12, IL28 and TLR4 and symptoms of congenital cytomegalovirus infection.
[PMID 32723620] Toll-like receptor gene polymorphisms in patients with keratitis.
[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.
