rs1800795

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.

This systematic review analyzed 24 studies examining 31 genes and 62 genetic variants associated with anterior cruciate ligament rupture (ACLR). Key findings show mixed evidence for collagen variants: COL1A1 rs1800012 showed protective association in European ancestry populations (OR=2.8, p=0.040), while COL1A2 rs42524 and rs2621215 conferred increased risk (OR=5.73 and 4.29 respectively). VEGFA polymorphisms rs2010963 and rs699947 showed conflicting associations across studies, and most major variants in IL6, IL1B, MMP genes, and inflammatory markers showed no consistent associations with ACLR across populations, highlighting the need for gender and ancestry-stratified analyses.

A case-control study of 273 DCM patients and 548 controls in the Chinese Han population examined seven genetic variants associated with cardiac neonatal lupus. The study found that the T allele of rs3134942 in NOTCH4 increased DCM risk by 61% (OR=1.61, 95% CI: 1.15-2.27, P=6.57×10⁻³) in additive and dominant models. Additionally, rs2472299 in CYP1A2 was associated with reduced DCM risk in the dominant model (OR=0.72, P=4.24×10⁻²) and correlated with smoking status in patients.

This case-control study of 1,088 Chinese Han women (360 cases, 728 controls) found that IL-6 gene polymorphisms rs1800795 and rs2069837 were significantly associated with cervical cancer risk, with adjusted OR 1.60 (95% CI 1.24-2.19) and 1.49 (95% CI 1.19-2.07) respectively. GMDR analysis revealed significant gene-gene interaction between these two SNPs (p=0.0010), with combined genotypes (GC/CC + AG/GG) conferring highest risk: OR 3.35 (95% CI 2.01-4.78).

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.

This PhD thesis investigated pharmacogenetics of microRNAs and immune system genes in locally advanced rectal cancer (LARC) patients treated with neoadjuvant chemoradiotherapy. In 265 LARC patients, five SNPs were identified as predictive biomarkers of pathological response: DROSHA-rs10719 (OR=1.87, p=0.0274) and SMAD3-rs17228212 (OR=2.01, p=0.0049) were unfavorable, while SMAD3-rs744910 (OR=0.45, p=0.0153), SMAD3-rs745103 (OR=0.48, p=0.0471), and TRBP-rs6088619 (OR=0.39, p=0.0125) were protective. In 235 LARC patients, three prognostic biomarkers for 2-year disease-free survival were identified: IL17F-rs641701 (HR=3.23, p=0.003), IL17F-rs9463772 (HR=2.89, p=0.002), and STAT3-rs8069645 (HR=0.50, p=0.044).

Two-stage case-control study (1,584 cervical cancer cases, 1,768 controls) in Eastern Chinese women found IL6 rs2069837 SNP associated with increased cervical cancer risk (OR 1.27, 95% CI 1.08-1.49, dominant model, p=0.004; OR 1.19, 95% CI 1.04-1.36, additive model, p=0.014). IL6 rs2069837 AG/GG carriers showed significantly higher IL6 protein expression levels than AA carriers. Evidence of gene-environment interaction with age at primiparity and menopausal status in cervical cancer development.

This systematic literature review examines interleukin and interleukin receptor gene polymorphisms associated with rheumatoid arthritis (RA) pathogenesis, diagnostics, and treatment. The paper summarizes polymorphisms in multiple IL genes (IL-1B rs16944, rs1143634; IL-6 rs1800795, rs1800796; IL-10 rs1800896; IL-23R rs11209026; IL-17A rs2275913 and others) across diverse populations, their associations with RA susceptibility and disease severity, and discusses current and future immunologic therapeutic targets including TNF inhibitors and IL-6 receptor antagonists.

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.

A case-control study of 483 postmenopausal women examined associations between three SNPs (rs3736228 and rs4988321 in LRP5, rs1800795 in IL-6) and osteoporosis/osteopenia at multiple skeletal sites using dual-energy X-ray absorptiometry and real-time PCR genotyping. LRP5 polymorphisms were significantly associated with osteoporosis at the lumbar spine (rs3736228 p=0.018, rs4988321 p=0.032) and proximal femur (rs3736228 p=0.008, rs4988321 p=0.003), while IL-6 rs1800795 GG genotype was a risk factor for hip osteoporosis (p=0.045 for genotypes). The findings support LRP5 and IL-6 polymorphisms as contributing to postmenopausal osteoporosis development.

PhD dissertation examining genetic variants in collagen genes (COL22A1, COL27A1, COL11A1) and anterior cruciate ligament injury risk in Polish athletes. Paper 1 is a systematic review of genetic determinants of ACL rupture. Papers 2 and 3 are case-control association studies finding no significant associations between SNPs rs11784270/rs6577958 (COL22A1), rs946053 (COL27A1), and rs3753841 (COL11A1) and non-contact ACL injury risk in Polish athletes.

Population-based case-control study of Connecticut women showing that genetic polymorphisms in IL10RA (rs9610) and TNF (rs1800629) genes modify the association between blood transfusion and non-Hodgkin lymphoma (NHL) risk. IL10RA rs9610 GG genotype carriers with transfusion history had increased NHL risk (OR=1.9, 95% CI: 1.1-3.2), while AG/AA carriers had decreased risk (OR=0.6, 95% CI: 0.4-0.9), with significant gene-transfusion interaction (P=0.003).

This genome-wide association study (GWAS) identified genetic variants influencing interleukin levels in African Americans. IL-10 levels showed genome-wide significant associations with 8 SNPs, most notably rs5743185 in PMS1 (p=2.30×10⁻¹⁰), with successful replication of rs17365948 in YWHAZ. IL-1Ra levels showed suggestive associations with SNPs in ASB3 and the IL-1 gene family, with replication of rs4251961. IL-6 levels showed genome-wide significant association with one variant near RP11-314E23.1 (p=8.63×10⁻⁹).

Turkish case-control study examining TRAIL and TRAIL-DR4 gene polymorphisms in gastric cancer. Compared TRAIL C1595T (rs1131580) and TRAIL-DR4 C626G (rs20575) genotype frequencies between 50 gastric cancer patients and 163 healthy controls. No significant association found between either polymorphism and gastric cancer risk (p>0.256, p>0.189) or clinical parameters including tumor stage, lymph node involvement, distant metastasis, and perineural invasion. Serum TRAIL levels were also not significantly different between groups (p>0.33).

A randomized controlled intervention study in 68 obese men tested the effects of polyphenol-rich cloudy apple juice (750 mL/day for 4 weeks) on obesity-related markers and diet-gene interactions. Cloudy apple juice significantly reduced percent body fat (Δ: -1.0 ± 1.3% vs control -0.2 ± 0.9%, p < 0.05) and increased lean body mass. The IL-6-174 G/C polymorphism (rs1800795) showed significant interaction with body fat reduction: only C/C carriers showed significant fat loss with apple juice consumption (p = 0.011 for interaction), while G/C and G/G carriers did not respond.

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 case-control study in 110 Croatian intravenous drug users with chronic hepatitis C found that rs1800795-IL6 C allele was significantly associated with sustained virological response (SVR) to pegylated interferon-alpha/ribavirin treatment (OR 2.15, 95% CI 1.16-4.68, p=0.019 after adjustment). Additionally, rs12979860-IL28B CC genotype showed a protective effect against chronic HCV acquisition (27% in patients vs 49% in population controls, p<0.001), suggesting a role in spontaneous HCV clearance.

A comprehensive review of nutrigenetics and nutrigenomics examining how genetic variants influence individual responses to nutrients and dietary interventions. The paper discusses associations between numerous SNPs (rs9939609 in FTO, rs2287019 in GIPR, rs7903146 in TCF7L2, rs5219 in KCNJ11, and many others) and metabolic traits including obesity, type 2 diabetes, and other chronic diseases, along with epigenetic mechanisms by which phytochemicals (curcumin, resveratrol, lycopene) modulate gene expression. The review synthesizes current evidence for precision nutrition approaches tailored to individual genetic profiles.

This PhD thesis comprises four association studies examining inherited variations in inflammatory cytokine genes and their pathogenetic role in rheumatoid arthritis (RA), multiple myeloma (MM), and B-cell non-Hodgkin's lymphoma (B-NHL). Paper I found that CHI3L1 promoter polymorphisms (rs4950928) were significantly associated with serum YKL-40 concentrations in 238 RA patients (P < 2.0e-16) and 605 controls. Paper IV reported CHI3L1 rs4950928 associated with follicular lymphoma 10-year overall survival (HRCG = 2.04, 95% CI 1.17-3.54). Papers II and III examined gene-gene interactions in MM and B-NHL risk and prognosis.

A population-based case-control study of 750 rectal cancer cases and 1205 controls examined associations between inflammation-related factors and specific rectal tumor mutations. IL6 rs1800796 polymorphisms, ibuprofen use, and dietary antioxidants were associated with TP53 mutations (OR 0.41 for alpha tocopherol, p trend 0.02; OR 0.51 for beta carotene, p trend 0.03), with stronger associations for TP53 transversion mutations. These findings support an inflammation-related pathway in rectal cancer development.

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 systematic literature review examines interleukin (IL) and interleukin receptor gene polymorphisms associated with rheumatoid arthritis (RA), covering studies from the past 10 years. The review discusses the pathogenesis of RA as a multifactorial autoimmune disease where genetic factors account for approximately 60% of disease risk. Multiple polymorphisms across IL-1, IL-2, IL-4, IL-6, IL-8, IL-10, IL-15, IL-17, IL-18, and IL-23R genes have been investigated in various populations, with inconsistent results across populations. The paper also reviews current and future therapeutic targets including anti-TNF, anti-IL-1, anti-IL-6, and anti-IL-17 treatments.

This study examined whether the effect of vitamin E supplementation on cytokine production in elderly nursing home residents depends on baseline cytokine levels. Among 110 elderly participants in a 1-year randomized controlled trial, the authors genotyped 7 SNPs in cytokine genes (IL-1β, IL-6, TNFα, IFNγ) and measured ex vivo cytokine production at baseline and follow-up. They found significant interactions between vitamin E treatment and baseline cytokine production for IFNγ (P=0.002-0.005), TNFα (P=0.009), IL-1β (P=0.053), and IL-6 (P=0.031), suggesting that vitamin E's immunomodulatory effects depend on individual baseline immune status.

This case-control study of 128 HCV-infected Brazilian patients and 94 healthy controls identified a significant association between TGFβ1 codon 25 (rs1800471) G allele and hepatitis C virus infection (P = 0.0005, OR = 2.9, 95% CI 1.6-5.6). The G/G genotype was significantly overrepresented in HCV patients (88.3% vs 68.1%, OR = 3.7, P = 0.0002). High-producing TGFβ1 phenotypes were also significantly associated with HCV infection (73.4% vs 52.1%, OR = 2.6, P = 0.0015). No associations were found with polymorphisms in TNFα, IFNγ, IL-10, TGFβ1 codon 10, or IL-6.

Fine-mapping study of C-reactive protein (CRP) regulation in 594 African Americans using dense SNP genotyping and Bayesian model selection. Found rs3091244(T) allele as the key functional variant regulating CRP expression with additive effects (Bayes factor >100), explaining 5.20% of CRP variance with β=0.312 (95% CI 0.146-0.491). Secondary analysis supported a two-SNP model including rs12728740, which segregated with European-origin haplotypes. The study demonstrates that weaker linkage disequilibrium in African Americans resolved genetic ambiguity seen in European populations.

A systematic review and meta-analysis of 161 published meta-analyses evaluating 344 gene-variant/cancer associations across 99 genes and 18 cancer sites. The authors calculated false-positive report probability (FPRP) values to evaluate the robustness of statistically significant findings (p<0.05). The most noteworthy associations at very low prior probability were GSTM1 null with bladder cancer (OR: 1.5, p=1.9×10-14), NAT2 slow acetylator with bladder cancer (OR: 1.46, p=2.5×10-7), MTHFR C677T with gastric cancer (OR: 1.52, p=4.9×10-8), and GSTM1 null with acute leukemia (OR: 1.20, p=8.6×10-15). Phase II metabolizing enzymes, particularly GSTM1 deletion, showed the most consistent and highly significant associations with cancer risk.

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).

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 cross-sectional study of 964 RA patients examined associations between genetic variants in IL-1, IL-6, IL-10, PTPN22, and SEPS with radiographic damage severity. IL-6 -174G allele showed allele-dose association with increased radiographic damage (P=0.005) specifically in RF-positive and anti-CCP-positive patients. Conversely, IL-10 -592CC genotype was associated with greater damage (P=0.006) but only in RF-negative and anti-CCP-negative patients. These associations were independent of autoantibody production.

A case-control study of 50 Egyptian children with rheumatic heart disease (RHD) and 98 controls examined associations between cytokine gene polymorphisms and RHD susceptibility and severity. TNFα -308 A/A homozygotes showed increased RHD risk (OR=5.7, p<0.001), IL-10 -1082 A/A and G/G genotypes were associated with disease (OR=3.1-5.2), and IL-1Ra A1/A1 showed increased frequency (OR=2.2, p<0.05). Composite high-risk genotypes (TNFα -308 A/A with IL-10 -1082 A/A, OR=37.4) were particularly associated with multivalvular disease. IL-6 -174 polymorphisms showed no significant association with RHD.

This journal issue contains multiple genetic association studies on rheumatoid arthritis (RA). A key REMARCA study (146 aCCP+ RA patients vs 314 controls) identified polymorphisms in CTLA4 (rs231775 +49A/G), IL10 (rs1800872 -592A/C), and IL6R (rs8192284 +358A/C) associated with high inflammatory disease activity, with CTLA4 and IL10 minor alleles showing increased risk (OR=1.4, p=0.02 and OR=1.9, p<0.0001 respectively) and IL6R minor allele being protective (OR=0.7, p=0.03). A separate study analyzed NOS3, PPARG, PPARGC1A, PPARGC1B and PAI1 polymorphisms in 73 RA patients for cardiovascular risk.

Candidate gene association study of 122 early rheumatoid arthritis (RA) patients and 314 healthy controls found that PTPN22 rs2476601 (OR=1.5, 95% CI 1.0-2.3, p=0.05) and TNFAIP3 rs675520 (OR=1.7) polymorphisms were significantly associated with RA risk. Anti-cyclic citrullinated peptide (ACPA) antibody production was associated with PTPN22, TNFAIP3, CTLA4, and TNF-α polymorphisms in a dose-dependent manner.

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 case-control study of 113 Kuwaiti Arab psoriatic arthritis (PsA) patients and 104 controls found significant associations between IL6 -174G/C (rs1800795, OR 2.22, p=0.02 for CC genotype) and TNF-alpha -308A/G (rs1800629, OR 3.91, p<0.0001 for G allele) polymorphisms and PsA susceptibility. IL13 R130Q (rs20541) showed no significant association. These findings suggest IL6 and TNF-alpha genetic variants contribute to genetic susceptibility to PsA in this population.

Case-control study of 60 Iranian asthmatic patients and 140 controls examining associations between proinflammatory cytokine gene polymorphisms and asthma susceptibility. TNFα -308 GA genotype was significantly associated with asthma (P=0.001), as were IL-1α TC at -889 (P=0.0001) and IL-1β TC at -511 (P=0.0001), while TNFα GG genotype was protective. The TNFα -308/-238 A/A haplotype was highly associated with asthma (P=0.0001).