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

Juan Jiao; Zhaoping Wang; Yanfei Guo; Jie Liu; Xiuqing Huang; Xiaolin Ni; Danni Gao; Liang Sun; Xiaoquan Zhu; Qi Zhou; Ze Yang; Huiping Yuan

doi:10.7717/peerj.12384

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

PeerJ. 2021 Oct 25:9:e12384. doi: 10.7717/peerj.12384. eCollection 2021.

Authors

Juan Jiao^#^{1

2}, Zhaoping Wang^#¹, Yanfei Guo³, Jie Liu², Xiuqing Huang¹, Xiaolin Ni¹, Danni Gao^{1

4}, Liang Sun¹, Xiaoquan Zhu¹, Qi Zhou¹, Ze Yang¹, Huiping Yuan¹

Affiliations

¹ The 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.
² Department of Clinical Laboratory, the Seventh Medical Center, Chinese PLA General Hospital, Beijing, China.
³ Department of Respiratory and Critical Care Medicine, Beijing Hospital, National Center of Gerontology; Institute of Geriatric Medicine, Chinese Academy of Medical Sciences, P.R. China.
⁴ Peking University Fifth School of Clinical Medicine (Beijing Hospital), Beijing, China.

^# Contributed equally.

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, I² 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.

Keywords: IL-1B (-511); IL-1RN (VNTR); Meta-analysis; Polymorphism; Type 2 diabetes mellitus.

Grants and funding

This work was supported by the National Natural Science Foundation of China (81870552, 81400790, 81600622, 81872096, 81571385, 91849118, 91849132, and 81600622), the National Key R&D Program of China (2018YFC2000400), Beijing Hospital Doctoral Scientific Research Foundation (BJ-2018-024), Beijing Hospital Nova Project (BJ-2018-139), and the Non-profit Central Research Institute Fund of Chinese Academy of Medical Sciences (2018RC330003). The funders had no role in study design, data collection and analysis, decision to publish, or preparation of the manuscript.