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Updated: Oct 14, 2025

Candidate Gene Testing in Clinical Cohort Studies with Multiplexed Genotyping and Mass Spectrometry
Published on: June 21, 2018
Association between IL-1B (-511)/IL-1RN (VNTR) polymorphisms and type 2 diabetes: a systematic review and
Juan Jiao1,2, Zhaoping Wang1, Yanfei Guo3
1The Key Laboratory of Geriatrics, Beijing Institute of Geriatrics, Institute of Geriatric Medicine, Chinese Academy of Medical Science, Beijing Hospital/National Center of Gerontology of National Health Commission, P.R. China.
Abstract:
Interleukin-1 (IL-1) plays an essential role in the immune pro-inflammatory process, which is regarded as one of many factors in the development of type 2 diabetes mellitus (T2DM). Several case-control studies have illustrated the association of the IL-1B (-511) (rs16944, Chr 2:112,837,290, C/T Intragenic, Transition Substitution) and IL-1RN (VNTR) (gene for IL-1 receptor antagonist, IL-1RA, 86 bp tandem repeats in intron 2) polymorphisms with T2DM risk. However, the results were inconsistent and inconclusive. We performed a meta-analysis (registry number: CRD42021268494) to assess the association of the IL-1B (-511) and IL-1RN (VNTR) polymorphisms with T2DM risk. Random-effects models were applied to calculate the pooled ORs (odds ratios) and 95% CIs (confidence intervals) to test the strength of the association in the overall group and subgroups stratified by ethnicity, respectively. Between-study heterogeneity and publication bias were evaluated by the Q-test, I statistic, Harbord test, and Peters test accordingly. Sensitivity analyses were also performed. A total of 12 publications evaluating the association of IL-1B (-511) and IL-1RN (VNTR) polymorphisms with the risk of T2DM development were included. The meta-analysis showed that IL-1RN (VNTR) was related to the increasing development of T2DM risk in the recessive model (OR = 1.62, 95% CI [1.09-2.42], P = 0.377, P = 0.018) and in the homozygous model (OR = 2.02, 95% CI [1.07-3.83], P = 0.085, P = 0.031), and the IL-1RN 2* allele was found a significant association with evaluated T2DM risk in all ethnicities (OR = 2.08, 95% CI [1.43-3.02], P < 0.001, P < 0.001) and in EA (OR = 2.01, 95% CI [1.53-2.66], P = 0.541, P < 0.001). Moreover, stratification by ethnicity revealed that IL-1B (-511) was associated with a decreased risk of T2DM in the dominant model (OR=0.76, 95% CI [0.59-0.97], P = 0.218, P z = 0.027) and codominant model (OR = 0.73, 95% CI [0.54-0.99], P = 0.141, P = 0.040) in the East Asian (EA) subgroup. Our results suggest that the IL-1RN 2* allele and 2*2* homozygous polymorphism are strongly associated with increasing T2DM risk and that the IL-1B (-511) T allele polymorphism is associated with decreasing T2DM risk in the EA subgroup.
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