Rs4986791

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]

[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