rs1143627 — IL1B -31T>C

IL-1 Beta Promoter -31T>C — Gastric Cancer, Periodontitis, and Amplified Inflammation

Interleukin-1 beta (IL-1β) is one of the most potent pro-inflammatory cytokines in the body — it initiates fever, activates immune cells, induces other cytokines, and drives inflammation in virtually every tissue. The rs1143627 variant sits just 31 base pairs upstream of the IL1B transcription start site, in a region that directly controls how vigorously your immune cells turn on IL-1β production. The IL1B gene sits on the minus strand¹¹ The IL1B gene sits on the minus strand
On the plus strand, this variant is G→A; the coding-strand notation -31T>C reflects the minus-strand complement.

The Mechanism

The -31 position lies within the TATA-box region of the IL1B promoter²² TATA-box region of the IL1B promoter
The TATA box is a core promoter element recognized by transcription factor TFIID, which recruits RNA polymerase to begin transcription. The T allele (A on the genomic plus strand) creates a binding site configuration that permits higher basal and stimulated IL-1β transcription. When macrophages and dendritic cells encounter bacteria, viruses, or crystals (such as urate or cholesterol), the T-allele variants mount a more vigorous IL-1β response — producing more cytokine for the same immune stimulus.

This promoter variant is in near-complete linkage disequilibrium with the -511C>T variant (rs16944)³³ near-complete linkage disequilibrium with the -511C>T variant (rs16944)
The two promoter SNPs are almost always inherited together as a haplotype, so their effects are highly correlated in most populations. However, rs1143627 sits closer to the transcription start site and may independently influence transcription factor binding at the TATA box.

The Evidence

The clearest association is with gastric cancer in the context of H. pylori infection. A meta-analysis of 37 studies (6,108 cases, 8,980 controls) found the -31T allele increases gastric cancer risk specifically in H. pylori-positive individuals⁴⁴ meta-analysis of 37 studies (6,108 cases, 8,980 controls) found the -31T allele increases gastric cancer risk specifically in H. pylori-positive individuals
Homozygous model: OR = 1.35 (95% CI 1.02-1.78); heterozygous model: OR = 1.31 (1.04-1.66); recessive model: OR = 1.29 (1.04-1.61). The interaction is mechanistically plausible: H. pylori triggers massive NLRP3 inflammasome activation, releasing IL-1β; the -31T variant amplifies this IL-1β surge, creating a chronically inflamed gastric mucosa that accelerates progression from gastritis to metaplasia to carcinoma.

At the tissue level, H. pylori-positive dyspepsia patients with the TT genotype had 2.25-fold higher odds of moderate-to-severe chronic antral inflammation compared to CC+CT carriers (80.8% vs. 65.2%, OR = 2.25, 95% CI 1.23-4.24, p = 0.005)⁵⁵ H. pylori-positive dyspepsia patients with the TT genotype had 2.25-fold higher odds of moderate-to-severe chronic antral inflammation compared to CC+CT carriers (80.8% vs. 65.2%, OR = 2.25, 95% CI 1.23-4.24, p = 0.005), directly demonstrating how the variant amplifies inflammatory damage in infected stomachs.

Chronic periodontitis shows a parallel pattern. In an Indian case-control study (157 periodontitis patients, 200 controls), IL1B -31C/T was significantly associated with increased susceptibility to chronic periodontitis⁶⁶ In an Indian case-control study (157 periodontitis patients, 200 controls), IL1B -31C/T was significantly associated with increased susceptibility to chronic periodontitis
The variant was also part of the optimal gene-gene interaction model for disease risk alongside IL1B +3954 and IL-10 -819. Bacteria in subgingival plaque trigger the same NLRP3-IL-1β axis that H. pylori activates in the stomach; genetically amplified IL-1β production accelerates periodontal bone destruction.

In Kawasaki disease, children under 12 months with the AA genotype at rs1143627 had 2.28-fold increased risk of coronary artery lesions (OR = 2.28, 95% CI 1.32-3.95, p = 0.0032), with the adjusted OR reaching 2.33 in 719 KD patients and 1,401 healthy controls from southern China ⁷⁷ children under 12 months with the AA genotype at rs1143627 had 2.28-fold increased risk of coronary artery lesions (OR = 2.28, 95% CI 1.32-3.95, p = 0.0032), with the adjusted OR reaching 2.33 in 719 KD patients and 1,401 healthy controls from southern China . This implicates high IL-1β production in amplifying the vasculitis that damages coronary arteries in this disease.

In transplantation immunology, rs1143627 was significantly associated with acute graft-versus-host disease grade II-IV in pediatric HSCT recipients (p = 0.019)⁸⁸ rs1143627 was significantly associated with acute graft-versus-host disease grade II-IV in pediatric HSCT recipients (p = 0.019)
Carriers of risk alleles combined with HLA-B*15:01 had hazard ratio 2.14 (95% CI 1.41-3.25, p = 6×10⁻⁶), confirming the variant's role in driving severe alloimmune inflammation.

Practical Actions

For carriers of the A allele (T in coding notation), the most actionable implications are:

Gastrointestinal health: H. pylori testing is especially important. If H. pylori is detected, eradication should be prompt and confirmed — the combination of this variant and active infection creates the gene-environment interaction that most dramatically elevates gastric cancer risk. After eradication, periodic upper endoscopy surveillance is warranted if there is a family history of gastric cancer or if atrophic gastritis was found.

Periodontal vigilance: The genotype amplifies periodontal inflammation in the presence of dysbiotic gingival flora. More frequent professional cleaning (every 3-4 months rather than 6) and diligent home plaque control directly reduce the bacterial trigger for IL-1β release.

Systemic inflammation monitoring: Elevated IL-1β drives IL-6 production, which raises hsCRP. Tracking high-sensitivity CRP as part of routine health assessments captures the downstream inflammatory state this variant promotes.

Interactions

This variant is in near-complete linkage disequilibrium with rs16944 (-511C>T), the other well-studied IL1B promoter polymorphism. They are typically inherited together as the -511T/-31T haplotype (A/A on the plus strand), which compounds expression effects. The IL-1 gene cluster also includes IL1A (rs1800587) and IL1RN (interleukin-1 receptor antagonist); variants in IL1RN that reduce the IL-1 receptor antagonist can amplify net IL-1β biological activity even further⁹⁹ variants in IL1RN that reduce the IL-1 receptor antagonist can amplify net IL-1β biological activity even further
IL-1Ra normally dampens IL-1β signaling by competitive receptor binding.