A strong role for the ABCG2 gene in susceptibility to gout in New Zealand Pacific Island and Caucasian, but not M(a)over-barori, case and control sample sets

作者：Phipps Green Amanda J; Hollis Moffatt Jade E; Dalbeth Nicola; Merriman Marilyn E; Topless Ruth; Gow Peter J; Harrison Andrew A; Highton John; Jones Peter B B; Stamp Lisa K; Merriman Tony R^*

来源：Human Molecular Genetics, 2010, 19(24): 4813-4819.

DOI：10.1093/hmg/ddq412

Genetic variation in ABCG2 (rs2231142, Q141K), encoding a uric acid transporter, is associated with gout in diverse populations. The aim of this study was to examine a role for ABCG2 in gout susceptibility in New Zealand M (a) over bar ori, Pacific Island and Caucasian samples. Patients (n = 185, 173 and 214, for M (a) over bar ori, Pacific Island and Caucasian, respectively) satisfied the American College of Rheumatology gout classification criteria. The comparison samples comprised 284, 129 and 562 individuals, respectively, without gout. rs2231142 was genotyped and stratification accounted for using genomic control markers. Association of the minor allele of rs2231142 with gout was observed in the Pacific Island samples (OR = 2.80, P-STRAT < 0.001 after accounting for effects of population structure), but not in the M (a) over bar ori samples (OR = 1.08, P-STRAT= 0.70), with heterogeneity in association evident between the M (a) over bar ori and Pacific Island datasets (P-HET = 0.001). A similar dichotomy in association was observed when samples were stratified into Western (Tonga, Samoa, Niue, Tokelau) versus Eastern Polynesian (M (a) over bar ori, Cook Island) origin (OR = 2.59, P-STRAT < 0.001; OR = 1.12, P-STRAT= 0.48, respectively; P-HET = 0.005). Association with gout was observed in the Caucasian samples (OR = 2.20, P = 3.2 x 10(-8)). Unlike SLC2A9, which is a strong risk factor for gout in both M (a) over bar ori and Pacific Island people, ABCG2 rs2231142 has a strong effect only in people of Western Polynesian ancestry. Our results emphasize the need to account for sub-population differences when undertaking biomedical genetic research in a group defined by a geographical region and shared ancestry but characterized by migratory events that create bottlenecks and altered genetic structure in the founder populations.

• 出版日期2010-12-15