rs4986791

Meta-analysis of 10 case-control studies (1476 UTI cases, 1449 controls) examining TLR4 gene polymorphisms rs4986790 and rs4986791 in relation to urinary tract infection risk. Overall analysis found no significant association; however, in Asian populations, rs4986790 G allele showed significant increased UTI risk (OR=1.88, 95% CI: 1.42-2.49 in allelic model; OR=1.97, 95% CI: 1.46-2.66 in dominant model).

This case-control study investigated the association between TLR2, TLR3, TLR4, and TLR9 polymorphisms and susceptibility to and prognosis of severe hepatitis among 135 newborn cases and 140 healthy controls of Chinese Han ethnicity. Certain SNPs were associated with disease risk and prognosis, including rs1898830 (TLR2; OR=0.38 for favorable prognosis in AG carriers), rs1879026 (TLR3; OR=0.29 for GT carriers), and rs187084 and rs352139 (TLR9). The haplotype A-C-G-G-C-A-T showed increased susceptibility (OR=4.11), while this haplotype was associated with favorable prognosis when present.

A genome-wide association study of 928 European Americans (81 cases with severe teenage acne, 847 controls) identified rs4133274 on chromosome 8q24 as significantly associated with severe teenage acne (OR=4.01, 95% CI=2.37-6.82, p=1.7×10⁻⁶), located 72 kb upstream of the MYC gene. The finding was not replicated in an independent cohort (n=1,392), but suggests a potential genetic link between acne and cancer risk through MYC-mediated androgen regulation.

A case-control genetic association study of 350 Czech patients undergoing total joint arthroplasty (98 with prosthetic joint infection, 252 without) plus 189 healthy controls investigated whether coding variants TLR2 R753Q (rs5743708), TLR4 D299G (rs4986790), and TLR4 T399I (rs4986791) contribute to prosthetic joint infection susceptibility. No significant differences in genotype or allele frequencies were found between infection cases and controls (p > 0.05), suggesting these TLR variants do not substantially affect prosthetic joint infection risk.

This case-control association study examined four TLR4 non-missense SNPs in 213 Chinese Han RA patients versus 247 controls. The 3' UTR SNP rs41426344 showed significant association with rheumatoid arthritis (C allele: OR=5.22, P=0.001; CC genotype: OR=3.94, P=0.009), as did rs7873784 (C allele: OR=1.54, P=0.028). Haplotype analysis identified H11 (CCGG) as protective and H5/H13 as risk haplotypes. The study demonstrates ethnic-specific allele frequency variation and suggests regulatory region polymorphisms play a role in RA susceptibility.

A systematic literature review examining the association between toll-like receptor (TLR) single nucleotide polymorphisms and susceptibility to hepatitis B virus (HBV) and hepatitis C virus (HCV) infection, including disease progression to liver cirrhosis and hepatocellular carcinoma. The review identifies polymorphisms in TLR2, TLR3, TLR4, TLR5, TLR7, TLR8, and TLR9 genes that affect viral susceptibility and disease outcomes, with mechanisms involving altered gene expression and immune signaling.

Population-based case-control study examining genetic variation in toll-like receptor genes (TLR2, TLR3, TLR4) and colon/rectal cancer risk and survival. TLR3 rs11721827 was associated with rectal cancer (OR 1.27, 95% CI 1.02-1.58), while TLR3 rs3775292 and TLR4 rs11536898 were associated with colon cancer (OR 0.68 and 0.50, respectively). Significant interactions were observed with NSAID use, smoking, and dietary factors. TLR2 rs5743704 and rs5743708 were associated with worse colon cancer survival (HRR 1.89 and 1.74, respectively).

This comprehensive review examines genetic polymorphisms in innate immune response genes that influence susceptibility to respiratory syncytial virus (RSV) infection and disease severity in children. The paper discusses key genes including TLR2, TLR3, TLR4, RIG-I, IL-8, RANTES/CCL5, NF-κB, AP-1, and vitamin D receptor (VDR), highlighting how SNPs such as TLR4 Asp299Gly and Thr399Ile, RANTES -28C/G, IL-8 -251T, and VDR FokI polymorphisms are associated with increased RSV susceptibility or protection in pediatric populations.

This candidate gene study of 1,817 participants from the ARIC Carotid MRI cohort identified genetic variants associated with monocyte activation markers. TLR2 rs1816702 was associated with increased CD14+/TLR2+ monocyte levels in whites (p<0.001), while TLR4 rs5030719 was associated with CD14+/TLR4+ levels in blacks (p<0.001). MPO gene variants also showed modest associations with monocyte MPO levels, demonstrating population-specific genetic influences on immune cell surface receptor expression.

This functional study demonstrated that cirrhosis-protective TLR4 SNPs rs4986790 (D299G) and rs4986791 (T399I) dampen inflammatory signaling and sensitize hepatic stellate cells to apoptosis, reducing fibrogenic responses. Cells expressing these SNPs showed reduced LPS responsiveness, decreased NFκB activation, lower Bcl-2 levels, reduced growth (P<0.05), and greatly increased spontaneous apoptosis (P<0.01) compared to wild-type TLR4, providing mechanistic evidence for how these variants protect against hepatic fibrosis.

A case-control study of 70 Caucasian breast cancer patients examined 8 germline polymorphisms in genes involved in oxidative stress protection, apoptosis, and DNA repair (TP53, NQO1, IL6, TLR4, XRCC1) to predict response to neoadjuvant anthracycline-based chemotherapy. Good pathological response (pCR or residual isolated invasive tumor cells) was significantly more frequent in ER/PR-negative tumors (43.5% vs 10.3% in ER/PR-positive, p=0.006) and G3 tumors (42.4% vs 6.3% in G1/G2, p=0.002). A non-significant trend toward good response was observed in TP53 Arg72Pro carriers (Arg/Arg or Arg/Pro) versus Pro/Pro homozygotes (37.9% or 17.6% vs 0%, p=0.071), and XRCC1 Arg194Trp heterozygotes showed decreased overall survival (HR=6.649, p=0.041).

This case-control study examined the role of CARD15, TLR4, SLC22A4/5, and DLG5 polymorphisms in 103 pediatric-onset and 696 adult-onset inflammatory bowel disease (IBD) patients compared to 272 healthy controls. CARD15 3020insC homozygosity was significantly more common in pediatric-onset Crohn's disease (CD) versus adult-onset CD (4.2% vs 0.6%, RR 7.1, 95% CI 1.2-42.0, P=0.04). SLC22A4/5 rs3792876 was significantly associated with pediatric-onset CD (6.1% vs 1.1% in adult-onset CD, P=0.02). DLG5 rs2165047 was associated with perianal disease in pediatric CD patients (RR 2.4, 95% CI 1.4-4.0, P=0.003).

This observational study of three cohorts (375 surgical patients, 159 ventilator-associated pneumonia patients, and 415 cardiac surgery patients) examined genetic variations in TLR4 (Asp299Gly/Thr399Ile, rs4986790 and rs4986791) and TIRAP/Mal (Ser180Leu, rs8177374) on sepsis susceptibility and cytokine response. Patients carrying mutations in both TLR4 and TIRAP/Mal showed significantly increased risk of severe infections (OR 5.5; P=0.02), as did TIRAP/Mal homozygous patients (OR 7.3; P<0.01), with reduced cytokine production in VAP patients but not in sterile inflammation.