rs4986790

This case-control study analyzes 28 SNPs in 26 inflammatory response genes in 343 patients (100 with appendicitis, 243 controls) using TaqMan genotyping. Significant associations were found for IL-13 rs1800925 (OR=6.02, 95% CI 1.52-23.78), IL-17 rs2275913 (OR=2.38, 95% CI 1.24-4.57), and CCL22 rs223888 (OR=0.12, 95% CI 0.02-0.90), suggesting a genetic-driven inflammatory response as a pathogenic mechanism in appendicitis.

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.

This prospective case-control study examined genetic variation in immune response genes and prostate cancer risk in the Prostate Cancer Prevention Trial (PCPT) placebo arm. Among 881 cases and 848 controls, the minor allele of rs3212227 in IL12(p40) was associated with increased prostate cancer risk (OR=1.30, 95% CI 1.10-1.53, P-trend=0.0017), particularly for lower-grade disease. The minor alleles of IL10 tagSNPs rs3021094 (OR=1.31, 95% CI 1.03-1.66, P-trend=0.03) and rs1800890 (OR=0.87, 95% CI 0.75-0.99, P-trend=0.04) showed significant associations. The study investigated whether observed associations were explained by PSA-associated detection bias and found that associations persisted in men with low PSA levels.

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.

This comprehensive review examines pattern recognition receptors (PRRs) and their role in immunosenescence and age-related diseases. The paper discusses how TLR and other PRR expression and function decline with aging, contributing to increased susceptibility to infections, reduced vaccine efficacy, and paradoxical chronic low-grade inflammation ('inflammaging'). The review also highlights associations between PRR gene polymorphisms and various diseases including cardiovascular disease, type 2 diabetes, cancer, and Alzheimer's disease.

This comprehensive review examines the genetic background of nonalcoholic fatty liver disease (NAFLD), focusing on variants identified by genome-wide association studies (GWAS) and candidate gene studies. The most significant GWAS-identified variants are PNPLA3 rs738409 (I148M), which strongly associates with increased liver steatosis, fibrosis severity, and HCC risk (12-fold increased risk for homozygous carriers), and TM6SF2 rs58542926 (E167K), which increases NASH progression but reduces cardiovascular risk. The review also discusses numerous candidate genes involved in lipid and glucose metabolism and liver injury mechanisms.

This PhD thesis by Paul Henderson comprises multiple studies on paediatric inflammatory bowel disease (PIBD) in Scotland, including epidemiological studies documenting a 76% rise in IBD incidence, genetic association studies identifying ICOSLG SNP rs8126734-A as overtransmitted in IBD/CD (p=0.0467, OR 1.85 for CD; p=0.0084), CRP gene variants rs1130864-A and rs1417938-A associated with PIBD susceptibility (OR 1.56-1.89 for CD), and functional characterization of NOD2 and autophagy pathways in Crohn's disease pathogenesis.

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.

This study investigated 34 SNPs in 18 Crohn's disease susceptibility genes in 62 pediatric CD patients and 46 controls with known Mycobacterium avium subspecies paratuberculosis (MAP) status. Mutations in TLR4 (rs4986790, Asp299Gly) and IL10RA (rs2229113, Gly330Arg) were significantly associated with MAP-positive CD (27.6% vs 6.1%, p=0.021 and 62.1% vs 33.3%, p=0.024, respectively), with a synergistic interaction (OR=7.39, 95% CI 2.25-24.27). Functional studies showed IL-10 and TNFα production were significantly lower in CD patients with NOD2 mutations, and IL10R and TLR4 receptor expression were elevated on NK cells and NK T cells harboring NOD2 mutations.

This case-control study examined the association between SNP polymorphisms in ERAP1, TGFB1, and TLR9 genes and ankylosing spondylitis (AS) susceptibility in a Chinese Han population (328 AS patients, 627 controls). Strong association was found for ERAP1 rs27044 (OR=3.88, P<0.0001), with the GG genotype conferring increased risk. No significant associations were observed for TGFB1 rs1800470 or TLR9 rs55704465, indicating that ERAP1 is a major non-HLA AS-associated locus in Chinese populations.

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.

Candidate gene association study of 67 genetic variants in 27 inflammation and DNA repair genes with hepatitis A virus (HAV) infection susceptibility in 6,779 NHANES III participants (2,619 non-Hispanic whites, 2,095 non-Hispanic blacks, 2,065 Mexican Americans). Among Mexican Americans, ABCB1 rs1045642 T allele was associated with lower HAV seropositivity risk (OR=0.79, p<0.001), while TGFB1 rs1800469 and XRCC1 rs1799782 T alleles were associated with increased risk (OR=1.38 and 1.57, respectively). CAT rs769214 and CYP2E1 rs2031920 showed marginal associations with decreased and increased HAV risk, respectively.

Comprehensive review of genetic background in nonalcoholic fatty liver disease (NAFLD). The PNPLA3 I148M variant (rs738409 C>G) is identified as a major genetic player strongly associated with increased liver fat content, NASH development, fibrosis severity, and HCC risk. The TM6SF2 E167K variant (rs58542926) emerges as another key contributor to NAFLD pathogenesis and disease progression. Multiple additional GWAS-identified variants and candidate genes are reviewed for their roles in NAFLD susceptibility and progression.

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.

Nested case-control study of 258 prostate cancer cases and 258 matched controls in the CLUE II prospective cohort examining genetic variants in inflammation and obesity-related genes. The IL10 -1082G>A variant (rs1800896, A allele) was positively associated with prostate cancer risk (AG vs GG: OR=1.69, 95% CI 1.10-2.60; AA vs GG: OR=1.81, 95% CI 1.11-2.96), while a TLR4 variant (rs4986790) showed inverse association, and no consistent associations were found for obesity-related gene variants.

This comprehensive review examines genetic associations in type I interferon-related signaling pathways across multiple autoimmune diseases. The authors review evidence linking dysregulated interferon alpha (IFNα) signaling to systemic lupus erythematosus (SLE), rheumatoid arthritis (RA), and other autoimmune conditions, identifying multiple susceptibility genes including IFIH1, IRF5, STAT4, TYK2, BLK, BANK1, FCGR2A, and TREX1 with well-replicated associations and functional relevance to IFN pathway dysfunction.

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).

PhD thesis describing comprehensive genome-wide association studies of acute anterior uveitis (AAU) in European (2,752 cases, 3,836 controls) and East Asian (821 cases, 4,898 controls) populations. European descent GWAS identified HLA-B at genome-wide significance plus 11 suggestive loci (ERAP1, NOS2, MERTK). East Asian GWAS identified HLA-B and ERAP1 at genome-wide significance plus 12 suggestive loci (GPR68, RHBDD2). Mendelian randomization confirmed ERAP1 as functionally relevant and showed genetically predicted CRP levels positively associated with AAU risk.

A case-control study of 127 multiple myeloma (MM) cases and 545 controls examined 82 common variants in 45 genes mediating immunity. IL4R rs2107356 (−28120T homozygotes, OR=1.91, 95% CI 1.08-3.38) and FCGR2A rs1801274 (−120G homozygotes, OR=1.95, 95% CI 1.06-3.60) were significantly associated with increased MM risk. A haplotype in the LTA*TNF complex (LTA −82C/−90G*TNF −1036C/−487G/−417G, OR=1.63, 95% CI 1.02-2.61) was also associated with increased MM risk compared to controls.

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).

A review article examining the genetic basis of COVID-19 susceptibility and protection from a longevity model perspective. The authors propose that genetic variants in the renin-angiotensin system (ACE, ACE2, AT1R, ANGIOTENSINOGEN), innate immunity genes (TLR4, CCR5, Connexin37), inflammatory cytokines (IL-6, IL-10, TNF-α, IFN-γ), and coagulation factors (PAI-1, Factor V) may influence COVID-19 outcomes, with long-lived individuals (nonagenarians/centenarians) serving as a model for identifying protective genetic profiles.

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.