Abstract
BackgroundSex-specific differences in the effect of genetic variants on serum urate levels have been described. The aim of this study was to systematically examine whether serum urate-associated genetic variants differ in their influence on gout risk in men and women.MethodsThis research was conducted using the UK Biobank Resource. Thirty single nucleotide polymorphisms (SNPs) associated with serum urate were tested for their association with gout in men and women of European ancestry, aged 40–69 years. Gene-sex interactions for gout risk were analysed using an interaction analysis in logistic regression models.ResultsGout was present in 6768 (4.1%) men and 574 (0.3%) women, with an odds ratio (95% confidence interval) for men 13.42 (12.32–14.62) compared with women. In men, experiment-wide association with gout was observed for 21 of the 30 serum urate-associated SNPs tested, and in women for three of the 30 SNPs. Evidence for gene-sex interaction was observed for ABCG2 (rs2231142) and PDZK1 (rs1471633), with the interaction in ABCG2 driven by an amplified effect in men and in PDZK1 by an absence of effect in women. Similar findings were observed in a sensitivity analysis which excluded pre-menopausal women. For the other SNPs tested, no significant gene-sex interactions were observed.ConclusionsIn a large population of European ancestry, ABCG2 and PDZK1 gene-sex interactions exist for gout risk, with the serum urate-raising alleles exerting a greater influence on gout risk in men than in women. In contrast, other serum urate-associated genetic variants do not demonstrate significant gene-sex interactions for gout risk.
Highlights
Sex-specific differences in the effect of genetic variants on serum urate levels have been described
When analysing for gene-sex interaction according to the number of effect alleles present, interaction was observed for ATP-binding cassette subfamily G member 2 (ABCG2) and PDZ domain containing 1 (PDZK1) in a similar pattern to that observed in the primary analysis (Fig. 3 and Additional file 1: Table S5). In this large population of European ancestry, we have identified gene-sex interactions for ABCG2 and PDZK1 for gout risk, with the serum urate-associated Single nucleotide polymorphism (SNP) exerting a greater influence on gout risk in men than in women
A genome-wide association studies (GWAS) by Dehghan et al [16] which included a total of 26,714 participants across the Framingham cohort study, the Rotterdam cohort study, and the Atherosclerosis Risk in Communities (ARIC) study demonstrated significant ABCG2 gene-sex interactions for serum urate in participants of the Framingham study and for participants of European ancestry from the ARIC study
Summary
Sex-specific differences in the effect of genetic variants on serum urate levels have been described. The aim of this study was to systematically examine whether serum urate-associated genetic variants differ in their influence on gout risk in men and women. Raised serum urate is the major risk factor for gout [5, 6]. Sex-specific analysis of genotypes associated with serum urate and gout have been examined. The magnitude of effect of the ABCG2 variant appears to be greater in men than women for both serum urate and gout risk [13, 16]. The SLC2A9 variant has been shown to exert greater influence for serum urate in pre-menopausal women compared with post-menopausal women and with men [17]
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
