Rs4986790

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]

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