Session Type: ACR Poster Session B
Session Time: 9:00AM-11:00AM
Background/Purpose: Gout results from formation of monosodium urate (MSU) crystals in the presence of hyperuricemia. Genome wide association studies have provided significant insights into hyperuricemia, however,the genetic basis of the progression from hyperuricemia to gout is still unclear. Previously, Chang et al (Rheumatology 2016;56:457-466) reported an association of the peroxisome proliferator-activated receptor gamma coactivator 1B (PPARGC1B) missense variant rs45520937 A-allele with gout risk in a Taiwan Han Chinese population (OR= 1.96, POR = 4.0 × 10−10) . PPARGC1B is a regulator of NOD-like receptor family pyrin domain containing 3 inflammasome (NLRP3)-activated inflammation. Our aim was to replicate the rs45520937 association in New Zealand (NZ) Polynesian (Māori and Pacific) and European ancestral groups to investigate the association of PPARGC1B variant with gout.
Methods: A total of 2645 clinically-ascertained gout cases based on American Rheumatism Association 1977 criteria and 2125 controls were utilized from the NZ population. There were 1143 Māori and Pacific (Polynesian) people with gout and 1241 without gout. The European data set was comprised of people with gout from Germany, The Netherlands and Scotland (n=571), and New Zealand (n=931) and 884 people without gout. Taqman® genotyping of PPARGC1B rs45520937 was undertaken, followed by multivariate-adjusted association analysis in R 3.2.2 version with gout as the outcome.
Results: The A-allele was at a lower prevalence in European controls compared to Polynesian controls (0.055 vs 0.418). The A-allele of rs45520937 was associated with increased risk of gout in the Polynesian sample set (OR= 1.17 [1.02-1.35], P=0.02) but not in the European sample set (OR=0.96 [0.73-1.27], P=0.81).
Conclusion: We replicated the association between the PPARGC1B risk A-allele of rs45520937 and gout in the NZ Polynesian group. However this association was not evident in the European group suggesting that this population-specific effect is restricted to the Asia-Pacific region. PPARGC1B is one of several inducible nodes, including PPARg and AMPK-activated protein kinase, in the complex regulatory network for damping NLRP3 inflammasome activation and the inflammatory arthritis phenotype in gout.
To cite this abstract in AMA style:Shaukat A, Jansen T, Janssen M, Joosten LAB, Radstake T, Riches P, Tausche AK, Harre Hindmarsh J, Dalbeth N, Stamp LK, Merriman TR. Replication of Genetic Association of Peroxisome Proliferator-Activated Receptor Gamma-1B with Gout in a New Zealand Polynesian Sample Set [abstract]. Arthritis Rheumatol. 2017; 69 (suppl 10). https://acrabstracts.org/abstract/replication-of-genetic-association-of-peroxisome-proliferator-activated-receptor-gamma-1b-with-gout-in-a-new-zealand-polynesian-sample-set/. Accessed June 17, 2021.
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ACR Meeting Abstracts - https://acrabstracts.org/abstract/replication-of-genetic-association-of-peroxisome-proliferator-activated-receptor-gamma-1b-with-gout-in-a-new-zealand-polynesian-sample-set/