rs1143634

This comprehensive literature review examines the role of interleukin-1 gene polymorphisms (IL1A and IL1B) in periodontitis susceptibility. Key findings indicate that rs1800587 and rs1143634 show the most consistent associations with periodontal disease across meta-analyses, though results vary significantly by ethnicity and population. Meta-analyses for rs1800587 show OR=1.22 for T allele in overall populations but significant association limited to Caucasians; rs1143634 shows OR=1.35-1.54 across multiple studies. Geographic and ethnic factors substantially influence genotype-disease correlations.

A case-control association study of 197 PTSD patients and 150 healthy controls in the Armenian population found that IL1B rs1143633 and rs16944 polymorphisms are protective against PTSD susceptibility. The rs1143633*C allele and rs16944*A allele had significantly lower frequencies in PTSD patients compared to controls (24% vs 39.7% and 21% vs 42%, respectively; OR=0.49 and OR=0.37). These findings suggest IL-1β genetic variants may modulate PTSD risk through effects on inflammatory response.

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 case-control study of 207 Iranian SLE patients and 213 healthy controls examined 5 SNPs in IL-1 family genes. The IL-1RN rs315952 CT genotype was significantly protective against SLE (OR=0.63, 95% CI=0.42-0.95, P<0.05), while the T allele was associated with hematologic manifestations in SLE patients (OR=1.75, 95% CI=1.07-2.84, P=0.033). No significant associations were found for IL-1A rs1800587, IL-1B rs16944, IL-1B rs1143634, or IL-1R1 rs2234650.

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.

First study evaluating the pharmacogenetic role of rs1143634 IL1B polymorphism and TNF promoter polymorphisms in infliximab-treated inflammatory bowel disease patients. Found rs1143634 C allele associated with higher serum IL1β concentrations (p=0.0345) and lower response to infliximab in Crohn's disease (p=0.027 for clinical remission). No significant associations found with TNF polymorphisms.

Genetic association study of cancer cachexia identified 129 SNPs in 80 candidate genes in 775 cancer patients. The C allele of rs6136 in the SELP gene (encoding P-selectin) was significantly associated with reduced risk of cancer cachexia (weight loss >10%) in both the main study (OR 0.52; p=0.026) and validation cohort (OR 0.09; p=0.035). Multiple other genes including APEH, GHRL, TNFRSF1A, and CNR1 showed significant associations with cachexia-related traits.

This case-control association study examined whether four coding SNPs in the IL-1 gene cluster (rs17561, rs1143634, rs419598, rs315952) are associated with Kawasaki disease (KD) susceptibility and coronary artery lesion (CAL) development in 109 Korean KD patients and 287 healthy controls. No significant associations were found between any of the four IL-1 cSNPs and KD or CAL development (all P > 0.05), suggesting the IL-1 gene cluster members are not genetic markers of KD susceptibility in the Korean population.

This comprehensive review examines the genomics of schizophrenia and pharmacogenomics of antipsychotic drugs, synthesizing evidence on over 200 genes associated with psychotic disorders. The authors discuss five categories of genes relevant to antipsychotic response: disease-associated genes, mechanism-of-action genes, drug metabolism genes (particularly CYP2D6, CYP2C19, CYP2C9, CYP3A4), drug transporter genes, and pleiotropic genes. The review details pharmacogenomic profiles of 20+ antipsychotic drugs and demonstrates significant ethnic and interindividual variation in drug metabolism phenotypes, with examples including CYP2D6 extensive metabolizers (55.71% of population), intermediate metabolizers (34.7%), poor metabolizers (2.28%), and ultra-rapid metabolizers (7.31%).

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.

Case-control study of 179 patients with chronic hyperplastic sinusitis with nasal polyposis (CHSwNP) and 153 controls examining 14 cytokine gene polymorphisms. The TNFα -308 SNP (rs1800629) was significantly associated with nasal polyposis susceptibility, with the A allele present in 18.6% of cases versus 11.5% of controls (odds ratio 1.86, 95% CI 1.14-3.09). All other cytokine polymorphisms tested were not statistically significant.

This prospective study of 316 HIV-positive adults identified genetic associations between inflammatory gene polymorphisms and Restless Legs Syndrome (RLS). Four IL1B SNPs (rs1143643, rs1143634, rs1143633, rs1071676) were significantly associated with RLS, with carriers of the minor allele having increased likelihood of RLS diagnosis (OR 2.56-10.3), explaining 15-17% of variance. IL17A rs8193036 was also significantly associated (OR 2.20, explaining 16% of variance) in adjusted logistic regression models.

Candidate gene case-control study in 221 Caucasian juvenile dermatomyositis (DM) patients versus 203 controls identified TNF-α and IL-1 cytokine polymorphisms as risk and protective factors. TNF-α -308AG (OR 3.6), TNF-α -238GG (OR 3.5), and IL-1α +4845TT (OR 2.2) increased DM risk, while TNF-α -308GG (OR 0.26) and TNF-α -238AG (OR 0.22) were protective. TNF-α -308AA was a risk factor for calcinosis (OR 7.3) and ulcerations (OR 7.0), with TNF-α -308G allele protective for both complications.

A comprehensive case-control and longitudinal cohort study of IL1A and IL1B polymorphisms in rheumatoid arthritis (RA) involving 3,561 patients and 3,062 controls across multiple populations. Despite strong suggestive findings in the discovery NARAC sample (RA3/A OR 1.27, P = 0.0021; RA4/C OR 1.56, P = 0.036), these associations failed replication in independent case-control cohorts and erosion status analyses, leading to the conclusion that common variants in IL1A/B do not significantly contribute to RA susceptibility or severity in European-descent populations.

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.

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.

Association study examining IL-1 gene polymorphisms (rs1800587 and rs1143634) in a coronary heart disease population (N=556). TT homozygotes at either SNP showed larger waist circumference (IL-1α: 1.8 cm greater, P=0.04; IL-1β: 4 cm greater, P=0.0004) compared to major allele homozygotes. The T:T haplotype carriers had 4.7 cm greater waist circumference (P=0.0001). Significant interaction between IL-1β SNP and BMI on waist circumference (P=0.01), with stronger effects in high BMI and high fibrinogen subgroups. Trend toward increased metabolic syndrome risk for IL-1β TT homozygotes (P=0.07).

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.

This computational modeling study examined IL-1 protein-receptor interactions in schizophrenia by analyzing genetic polymorphisms associated with the disease. The authors identified and analyzed 12 SNPs in IL-1 pathway genes (IL-1α, IL-1β, IL-1RA) and modeled their structural effects. The key finding was that rs315952 (p.Ser130Arg in IL-1RA) leads to weakened binding of IL-1RA to IL-1 receptors, potentially triggering the IL-1 signaling pathway and contributing to schizophrenia pathogenesis through dysregulated immune response.

A case-control study of 102 patients with symptomatic hip/knee arthroplasty (SA) and 93 asymptomatic controls examining IL-1 gene polymorphisms found that the IL1RN VNTR 498bp allele was significantly associated with SA complications (37% vs 11%, p<0.0001). In patients with atopy, the association was even stronger (60% vs 10%, p<0.000001), with 4-fold increased risk of SA complications. No significant associations were found for IL-1B polymorphisms (-3954, -511, -31) with the complications.