Person:

Choi, Hyon

Deposition of crystallized monosodium urate (MSU) in joints as a result of hyperuricemia is a central risk factor for gout. However other factors must exist that control the progression from hyperuricaemia to gout. A previous genetic association study has implicated the toll-like receptor 4 (TLR4) which activates the NLRP3 inflammasome via the nuclear factor-κB signaling pathway upon stimulation by MSU crystals. The T-allele of single nucleotide polymorphism rs2149356 in TLR4 is a risk factor associated with gout in a Chinese study. Our aim was to replicate this observation in participants of European and New Zealand Polynesian (Māori and Pacific) ancestry. A total of 2250 clinically-ascertained prevalent gout cases and 13925 controls were used. Non-clinically-ascertained incident gout cases and controls from the Health Professional Follow-up (HPFS) and Nurses Health Studies (NHS) were also used. Genotypes were derived from genome-wide genotype data or directly obtained using Taqman. Logistic regression analysis was done including age, sex, diuretic exposure and ancestry as covariates as appropriate. The T-allele increased the risk of gout in the clinically-ascertained European samples (OR = 1.12, P = 0.012) and decreased the risk of gout in Polynesians (OR = 0.80, P = 0.011). There was no evidence for association in the HPFS or NHS sample sets. In conclusion TLR4 SNP rs2143956 associates with gout risk in prevalent clinically-ascertained gout in Europeans, in a direction consistent with previously published results in Han Chinese. However, with an opposite direction of association in Polynesians and no evidence for association in a non-clinically-ascertained incident gout cohort this variant should be analysed in other international gout genetic data sets to determine if there is genuine evidence for association.

Background: Prior qualitative research on gout has focused primarily on barriers to disease management. Our objective was to use patients’ perspectives to construct an explanatory framework to understand how patients become engaged in the management of their gout. Methods: We recruited a sample of individuals with gout who were participating in a proof-of-concept study of an eHealth-supported collaborative care model for gout involving rheumatology, pharmacy, and dietetics. Semistructured interviews were used. We analyzed transcripts using principles of constructivist grounded theory involving initial coding, focused coding and categorizing, and theoretical coding. Results: Twelve participants with gout (ten males, two females; mean age, 66.5 ± 13.3 years) were interviewed. The analysis resulted in the construction of three themes as well as a framework describing the dynamically linked themes on (1) processing the diagnosis and management of gout, (2) supporting management of gout, and (3) interfering with management of gout. In this framework, patients with gout transition between each theme in the process of becoming engaged in the management of their gout and may represent potential opportunities for healthcare intervention. Conclusions: Findings derived from this study show that becoming engaged in gout management is a dynamic process whereby patients with gout experience factors that interfere with gout management, process their disease and its management, and develop the practical and perceptual skills necessary to manage their gout. By understanding this process, healthcare providers can identify points to adapt care delivery and thereby improve health outcomes.