Association between IL-1B (-511)/IL-1RN (VNTR) polymorphisms and type 2 diabetes: a systematic review and meta-analysis

• Published in: PeerJ (San Francisco, CA) Vol. 9; p. e12384
• Main Authors: Jiao, Juan, Wang, Zhaoping, Guo, Yanfei, Liu, Jie, Huang, Xiuqing, Ni, Xiaolin, Gao, Danni, Sun, Liang, Zhu, Xiaoquan, Zhou, Qi, Yang, Ze, Yuan, Huiping
• Format: Journal Article
• Language: English
• Published: San Diego PeerJ. Ltd 25.10.2021; PeerJ, Inc; PeerJ Inc
• Subjects: Alleles; Analysis; Apoptosis; Cardiovascular disease; Cytokines; Development and progression; Diabetes; Diabetes and Endocrinology; Diabetes mellitus (non-insulin dependent); Diabetes therapy; Epidemiology; Ethnicity; Genes; Genetic aspects; Glucose; IL-1B (-511); IL-1RN (VNTR); IL-1β; Inflammation; Insulin resistance; Interleukin 1; Interleukin 1 receptor antagonist; Interleukins; Medical Genetics; Meta-analysis; Minority & ethnic groups; Polymorphism; Registered nurses; Sensitivity analysis; Systematic review; Type 2 diabetes; Type 2 diabetes mellitus; China
• ISSN: 2167-8359; 2167-8359
• DOI: 10.7717/peerj.12384

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 2 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 het = 0.377, P z = 0.018) and in the homozygous model (OR = 2.02, 95% CI [1.07–3.83], P het = 0.085, P z = 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 het < 0.001, P z < 0.001) and in EA (OR = 2.01, 95% CI [1.53–2.66], P het = 0.541, P z < 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 het = 0.218, P z = 0.027) and codominant model (OR = 0.73, 95% CI [0.54–0.99], P het = 0.141, P z = 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.