Gout & GLUT9 Gene

Session: Crystal Associated Arthropathies

Presentation: 1943 – The GLUT9 Gene and Susceptibility to Gout in the New Zealand Population

Category: 14. Metabolic and crystal arthropathies

Author(s): Nicola Dalbeth1, Jade E. Hollis-Moffat2, Xin Xu2, Marilyn Merriman2, Peter Gow1, Andrew Harrison2, John Highton2, Peter B B Jones1, Lisa K. Stamp2, Tony Merriman2. 1University of Auckland, Auckland, New Zealand; 2University of Otago, Dunedin, New Zealand

Abstract:
Background/purpose: New Zealand Maori and Pacific men have the highest reported prevalence rates of gout worldwide (10-15%). Renal under-excretion of uric acid is a primary gout-causing checkpoint in people of Maori and Pacific ancestry. The genetic basis to gout is poorly defined, although genome-wide association scanning has revealed consistent genetic association of the glucose transporter GLUT9 (SLC2A9) gene with serum urate levels and gout in several Caucasian populations. The minor allele of a GLUT9 marker (rs5028843) is protective of gout. The aim of this study was to examine the role of GLUT9 in gout susceptibility in three major populations of New Zealand; Maori, Pacific and Caucasian.

Methods: Patients with gout (cases) were recruited from hospital outpatient clinics in the cities of Auckland, Wellington and Christchurch (New Zealand). The cases comprised of 82 of Caucasian ancestry, 32 of Maori ancestry, and 68 of Pacific ancestry. All cases had rheumatologist-confirmed gout and satisfied the American College of Rheumatology diagnostic criteria for acute gout. The control cohort comprised 554 of Caucasian descent, 75 of Maori descent and 45 of Pacific descent, who did not have a self-reported history of arthritis or gout. GLUT9 single nucleotide polymorphism rs5028843 was genotyped over the three case-control cohorts (Table).

Results: Association to gout was replicated in the Caucasian case-control cohort (OR allele 2 = 0.52; P=0.004). None of the Maori or Pacific cases with gout possessed the minor allele (allele 2). There was a significant difference in allele frequency within both the Maori (P=0.0003) and Pacific (P=0.002) cohorts. The observation that all Maori and Pacific controls who reported four grandparents of Polynesian descent (n=29) were homozygous for allele 1, suggests that the presence of allele 2 in the other Maori and Pacific control individuals is due to Caucasian admixture in the Maori and Pacific populations.

Conclusions: This work has confirmed the role of GLUT9 in gout susceptibility in people of Caucasian ancestry in New Zealand. Given the admixture with Caucasian that is known to exist in the New Zealand Maori and Pacific populations, it is possible that the apparent association with gout in these cohorts is a reflection of admixture introducing allele 2 of rs5028843 into the control cohorts. These data suggest that the inherent hyperuricaemia present in the modern Maori and Pacific populations can be partly explained by the very low frequency (or absence) of allele 2 of rs5028843 in the ancestral Maori and Pacific populations.

rs5028843 distribution in New Zealand gout case and control cohorts
	Allele 2	Genotype; Freq (individuals)
	Freq (# Chrs)	22	12	11
Caucasian
Case	0.152 (25)	0.049 (4)	0.207 (17)	0.744 (61)
Control	0.255 (283)	0.061 (34)	0.388 (215)	0.551 (305)
Maori
Case	0 (0)	0 (0)	0 (0)	1.0 (32)
Control	0.180 (27)	0.040 (3)	0.280 (21)	0.680 (51)
Pacific
Case	0 (0)	0 (0)	0 (0)	1.0 (68)
Control	0.067 (6)	0.022 (1)	0.089 (4)	0.889 (40)

Research Method: Basic
Type of Trial: Correlative
Phase: Other