Epidermal growth factor gene is a newly identified candidate gene for gout.

Lin Han,Can Wang,Chunwei Cao,Xuefeng Wang,Shiguo Liu,Changgui Li,Ruosai Xin,Wei Ren,Zhen Liu,Zhaotong Jia,Xinde Li

doi:10.1038/srep31082

Abstract

Chromosome 4q25 has been identified as a genomic region associated with gout. However, the associations of gout with the genes in this region have not yet been confirmed. Here, we performed two-stage analysis to determine whether variations in candidate genes in the 4q25 region are associated with gout in a male Chinese Han population. We first evaluated 96 tag single nucleotide polymorphisms (SNPs) in eight inflammatory/immune pathway- or glucose/lipid metabolism-related genes in the 4q25 region in 480 male gout patients and 480 controls. The SNP rs12504538, located in the elongation of very-long-chain-fatty-acid-like family member 6 gene (Elovl6), was found to be associated with gout susceptibility (Padjusted = 0.00595). In the second stage of analysis, we performed fine mapping analysis of 93 tag SNPs in Elovl6 and in the epidermal growth factor gene (EGF) and its flanking regions in 1017 male patients gout and 1897 healthy male controls. We observed a significant association between the T allele of EGF rs2298999 and gout (odds ratio = 0.77, 95% confidence interval = 0.67–0.88, Padjusted = 6.42 × 10−3). These results provide the first evidence for an association between the EGF rs2298999 C/T polymorphism and gout. Our findings should be validated in additional populations.

Highlights

Gout is a common form of arthritis caused by the deposition of monosodium urate crystals in joints, and it affects 1–2% of adults in developed countries[1]
In the first stage of analysis, 96 tag single nucleotide polymorphisms (SNPs) in the eight candidate genes in the 4q25 region were genotyped in 480 male gout patients and 480 matched controls (Supplementary Table S1)
SNPs with call rates below 90% and PHWE < 0.001 were excluded from subsequent analysis

Summary

Introduction

Gout is a common form of arthritis caused by the deposition of monosodium urate crystals in joints, and it affects 1–2% of adults in developed countries[1]. In recent genome-wide association studies (GWAS), several hyperuricemia and gout susceptibility genes have been identified[5,6,7,8,9,10,11], including the major urate loci solute carrier family 2 (facilitated glucose transporter), member 9 (SLC2A9) and ATP-binding cassette, sub-family G (ABCG2)[9,12]. We have conducted a multistage GWAS in the Han Chinese population and have identified three new risk loci, 17q23.2 (BCAS3), 9p24.2 (RFX3), and 11p15.5 (KCNQ1), which are most likely related to progression from hyperuricemia to inflammatory gout[13] Despite this progress, it is likely that many other unidentified genes contribute to the formation of monosodium urate crystals and clinical presentation of acute gout arthritis and chronic tophaceous disease. We speculate that a certain gene in 4q25 region may play a role in gout susceptibility

Methods

Results

Conclusion