Arthritis & Rheumatism, Volume 60,
October 2009 Abstract Supplement
The 2009 ACR/ARHP Annual Scientific Meeting
Philadelphia October 16-21, 2009.
A Strong Role for the ABC-Binding Cassette G2 (ABCG2) Gene in Susceptibility to Gout in New Zealand Western Polynesian, but Not Eastern Polynesian (Mori), Cases and Controls
Merriman1, Tony R., Dalbeth2, Nicola, Phipps-Green1, Amanda, Merriman1, Marilyn, Topless, Ruth, Gow3, Peter, Harrison1, Andrew
New Zealand (NZ) Maori and Pacific Island men have the highest reported rates of gout. Genetic variation in ABC efflux transporter G2 (ABCG2), a renal urate transporter, is convincingly associated with gout in Caucasian, with the non-synonymous single nucleotide polymorphism (SNP) Q141K (rs2231142) the likely etiological variant. The aim of this study was to examine a role for ABCG2 in susceptibility to gout in three NZ cohorts (of Maori, Pacific Island and Caucasian ancestry).
Patients that satisfied the ACR classification criteria for gout (n=55, 102 and 171, for Maori, Pacific Island and Caucasian respectively) were recruited from rheumatology outpatient clinics. The control samples were comprised of 89, 41 and 555 individuals, respectively, without arthritis. SNP rs2231142 was genotyped using Taqman. Population stratification in the Maori and Pacific Island analyses was accounted for using genomic control markers together with STRUCTURE and STRAT software.
Strong association of the minor allele of rs2231142 with gout was observed in the Pacific Island samples (OR = 4.13, P= 9.8 × 10-6) but not in the Maori samples (OR = 1.59, P= 0.25). Similar results were evident after accounting for population structure (PMaori= 0.15; PPacific < 0.001). Within the Pacific Island case samples there was a region-specific effect; 93 % of the risk allele positive individuals were Western Polynesian (Samoa, Tonga, Niue, Tokelau), compared to 58% of the risk allele negative individuals, with the remainder Eastern Polynesian (Cook Islands); P= 2 × 10-5. The genotype distribution in the Cook Island Maori cases (1,1 = 74%; 1,2 = 26%; 2,2 = 0%) was similar to that observed in the NZ Maori cases. Association with gout was also seen in the Caucasian samples (OR = 2.00, P= 9.7 × 10-6).
|Genotype (n, freq)|
|Cohort||1/1||1/2||Minor allele (n, freq)||OR [95% CI]||Pallelic||Pstrat||2/2|
|Case||35 (0.686)||16 (0.314)||0 (0.000)||16 (0.157)||1.59 [0.763.31]||0.25||0.15|
|Control||64 (0.790)||17 (0.210)||0 (0.000)||17 (0.105)|
|Case||33 (0.327)||43 (0.426)||25 (0.248)||93 (0.460)||4.13 [2.148.00]||9.8 × 10-6||<0.001|
|Control||25 (0.658)||13 (0.342)||0 (0.000)||13 (0.171)|
|Case||101 (0.601)||59 (0.351)||8 (0.048)||75 (0.223)||2.00 [1.472.73]||9.7 × 10-6|||
|Control||429 (0.763)||125 (0.222)||8 (0.014)||141 (0.125)|
Our data confirm a role for ABCG2 in gout susceptibility in NZ Pacific Island and Caucasian sample sets. Unlike the situation at SLC2A9 where the Caucasian-associated variants are considerably stronger risk factors for gout in both Maori and Pacific Island people than in Caucasian, the ABCG2 Q141K variant has a stronger effect only in Pacific Island people. The reason for this could be genetic difference between Western and Eastern Polynesian populations.
To cite this abstract, please use the following information:
Merriman, Tony R., Dalbeth, Nicola, Phipps-Green, Amanda, Merriman, Marilyn, Topless, Ruth, Gow, Peter, et al; A Strong Role for the ABC-Binding Cassette G2 (ABCG2) Gene in Susceptibility to Gout in New Zealand Western Polynesian, but Not Eastern Polynesian (Mori), Cases and Controls [abstract]. Arthritis Rheum 2009;60 Suppl 10 :1506