Role of the urate transporter SLC2A9 gene in susceptibility to gout in New Zealand Māori, Pacific Island, and Caucasian case–control sample sets

Abstract

Objective. To examine the role of genetic variation in the renal urate transporter SLC2A9 in gout in New Zealand sample sets of Māori, Pacific Island, and Caucasian ancestry and to determine if the Māori and Pacific Island samples could be useful for fine-mapping.Methods. Patients (n‫؍‬ 56 Māori, 69 Pacific Island, and 131 Caucasian) were recruited from rheumatology outpatient clinics and satisfied the American College of Rheumatology criteria for gout. The control samples comprised 125 Māori subjects, 41 Pacific Island subjects, and 568 Caucasian subjects without arthritis. SLC2A9 single-nucleotide polymorphisms rs16890979 (V253I), rs5028843, rs11942223, and rs12510549 were genotyped (possible etiologic variants in Caucasians).Results. Association of the major allele of rs16890979, rs11942223, and rs5028843 with gout was observed in all sample sets (P ‫؍‬ 3.7 ؋ 10 ؊7 , 1.6 ؋ 10 ؊6 , and 7.6 ؋ 10 ؊5 for rs11942223 in the Māori, Pacific Island, and Caucasian samples, respectively). One 4-marker haplotype (1/1/2/1; more prevalent in the Māori and Pacific Island control samples) was not observed in a single gout case.Conclusion. Our data confirm a role of SLC2A9 in gout susceptibility in a New Zealand Caucasian sample set, with the effect on risk (odds ratio >2.0) greater than previous estimates. We also demonstrate association of SLC2A9 with gout in samples of Māori and Pacific Island ancestry and a consistent pattern of haplotype association. The presence of both alleles of rs16890979 on susceptibility and protective haplotypes in the Māori and Pacific Island sample is evidence against a role for this nonsynonymous variant as the sole etiologic agent. More extensive linkage disequilibrium in Māori and Pacific Island samples suggests that Caucasian samples may be more useful for fine-mapping.Gout is the most common form of arthritis affecting men, occurring in 1-2% of Caucasian men in Westernized countries. In New Zealand, gout affects 9.3-13.9% of Māori men and 14.9% of Pacific Island men (1,2). Māori and Pacific Island populations also have high rates of severe gout, with frequent tophaceous disease and accelerated joint damage (3,4). The central cause of gout is hyperuricemia, which leads to the deposition of monosodium urate crystals within joints and tissue; in some gout patients this is followed by the development of an inflammatory response to the urate crystals and an attack of acute gout. Renal underexcretion of uric acid has been demonstrated to be a primary gout-determining checkpoint in Māori and Pacific Island people (5-7).

A qualitative study to explore health professionals’ experience of treating gout: understanding perceived barriers to effective gout management

“…23 Due to genetic factors, Māori and Pacific Island patients have a predisposition towards poor excretion of uric acid, and knowledge of this may help destigmatise gout in this group. 1 Genetic risk was not mentioned by our interviewees as a barrier to optimal gout treatment, highlighting the importance of improving and supporting cultural competence among clinicians to overcome perceived cultural barriers. Through this lens, clinicians are responsible for knowing their own culture, and differences between their culture and their patients'.…”

“…In New Zealand (NZ), many Māori and Pacific Island men have a genetic predisposition to gout and experience more severe and debilitating disease. [1][2][3] The most recent epidemiological data show that gout prevalence in Māori and Pacific Island males aged 65 years is more than 30%. 4 Acute gout attacks are self-limiting and can be treated with non-steroidal anti-inflammatories (NSAIDs) colchicine or prednisone.…”

Biological Anthropology in the Indo-Pacific Region: New Approaches to Age-Old Questions

“…Historical research (Gosling et al, 2014b) combined with palaeopathological identification of diagnostic lesions (Buckley, 2011;Buckley, 2007;Snow, 1974) has established a deep time-depth for these conditions. It has therefore been proposed that the high rates of disease in modern populations may be a result of ancestry and an inherited genetic predisposition to disease (Hollis-Moffatt et al, 2009;Phipps-Green et al, 2010). These findings have been valuable in initiating discussions with communities about this disease burden and promoting education through community initiatives such as the Māori Gout Action Group (Winnard et al, 2008).…”

Gout: The King of Diseases and the Disease of Kings

“…A polymorphism of this gene has been associated with under-excretion of uric acid and hyperuricemia in German Caucasians [10] and a mutation in the gene coding for URAT-1 has been shown to be protective for development of gout in a Japanese cohort [11]. Furthermore, an association of SLC2A9 [12] with gout has been demonstrated in samples of Maori population.…”