Associations between interleukin and interleukin receptor gene polymorphisms and risk of gout.

Shiguo Liu,Nan Chu,Can Wang,Zheng Zhou,Mingzhen Guo,Changgui Li

doi:10.1038/srep13887

Abstract

Gout is a self-limiting, auto-inflammatory arthritis induced by the deposition of monosodium urate crystals in the synovial fluid and periarticular tissues. The aim of this study was to investigate the associations between genetic variants in the interleukin (IL) and interleukin receptor (ILR) genes IL-33, IL-1RL1, IL-23R, and signal transducer and activator of transcription 4 (STAT4) and susceptibility to gout in Chinese Han male individuals. The genetic distributions of rs3939286 in IL-33, rs13015714 in IL-1RL1, rs10889677 in IL-23R, and rs7574865 in STAT4 were detected in 1100 men with gout and 1227 ethnically matched controls, using Taqman allelic discrimination real-time polymerase chain reaction (PCR). Differences in these polymorphisms between the groups were investigated using χ2 tests. The genotype-phenotype relationship among gout patients was tested by analysis of variance. There was a significant difference in genotypic frequencies of IL-23R rs10889677 between gout patients and controls (χ2 = 81.386, P < 0.001). However, there were no significant differences in distributions of the other polymorphisms between the groups. Our results revealed that the rs10889677 variant in IL-23R may be involved in the development of gout in Chinese Han male individuals. However, further studies in other ethnic groups are needed to confirm these results.

Highlights

The IL-33/IL-1RL1 axis plays a critical role in several autoimmune and inflammatory disorders
Gouty inflammation is a paradigm of innate immunity and the IL-1β /IL-1R pathway plays a key role in acute gout attack[16]
Phagocytosis of monosodium urate crystals (MSU) by macrophages can activate the NLRP3 inflammasome, which is considered to play a critical role in gouty arthritis

Summary

Introduction

The IL-33/IL-1RL1 axis plays a critical role in several autoimmune and inflammatory disorders. After binding to the IL-23 receptor (IL-23R), IL-23 stimulates the secretion of a variety of inflammatory factors such as IL-1, IL-6, IL-8, and TNF-α by activated CD4 + Th17 cells, which in turn drive gouty inflammation[13]. Signal transducer and activator of transcription 4 (STAT4), encoded by STAT4 mapped to chromosome 2q33, regulates the IL-23-related inflammatory response by transmitting signals in response to several cytokines such as IL-23 and IL-1214. STAT4 is essential for the expansion of Th17 cells activated by IL-23, which contributes to the development of many autoimmune diseases[15]. The production and function of cytokines may be affected by polymorphisms in the functional regions of their genes, suggesting that IL-33, IL-1RL1, IL-23R, and STAT4 may be candidate genes for the inflammatory pathogenesis of gout. The current study aimed to investigate the associations between the IL-33 rs3939286 A/G, IL-1RL1 rs13015714 G/T, IL-23R rs10889677 A/C, and STAT4 rs7574865 G/T single nucleotide polymorphisms (SNPs) and the risk of gout

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Conclusion