Arthritis & Rheumatism, Volume 63,
November 2011 Abstract Supplement

Abstracts of the American College of
Rheumatology/Association of Rheumatology Health Professionals
Annual Scientific Meeting
Chicago, Illinois November 4-9, 2011.


Association with Gout of PDZK1 Variants That Influence Metabolic Traits and Serum Urate Levels.

Merriman1,  Tony R., Dalbeth2,  Nicola, Hollis-Moffatt1,  Jade E., Phipps-Green1,  Amanda, Topless1,  Ruth, Merriman1,  Marilyn E., Gow3,  Peter J.

University of Otago, Dunedin, New Zealand
University of Auckland, Auckland, New Zealand
Middlemore Hospital, Auckland, New Zealand
Hutt Hospital, Lower Hutt, New Zealand
Univ of Otago Med Sch, Dunedin, New Zealand
Waikato Clinical School, Waikato Hospital, Hamilton, New Zealand
University of Otago, Christchurch, Christchurch, New Zealand

Background/Purpose:

Hyperuricemia is an independent risk factor for the development of gout. Gout is associated with obesity, insulin resistance, type 2 diabetes and cardiovascular disease. Genome wide association studies have identified variants in PDZK1 that regulate serum urate levels (Yang et al. Cardiovasc Circ Genet 2010;3:523–30), and PDZK1 variants have also been associated with the metabolic syndrome (Junyent M et al. J Nutr 2009;139:842–8). However, despite influencing serum urate levels at a genome-wide level, there was no evidence for association with gout in 1,100 cases and 27,183 controls (Yang et al. 2010). This may be due to the inclusion of cases taking diuretics. Significantly, the same allele of PDZK1 variant rs1967017 that is associated with increased serum urate levels is associated with reduced blood pressure (van der Harst et al. Hum Mol Genet 2010;19:387–92). Our aim was to use a case-control approach to examine the effects of PDZK1 variants on the risk of gout development in New Zealand (NZ) in sample sets with cases taking diuretics excluded.

Methods:

Patients were 328 Caucasians, 280 Eastern Polynesian (NZ Maori and Cook Island), and 249 Western Polynesians (Tonga, Samoa, Niue, Tokelau). Controls were 641 Caucasians, 348 Eastern Polynesians, and 144 Western Polynesians. Cases, recruited within New Zealand, were ascertained by American College of Rheumatology classification criteria, with exclusion of cases taking diuretic medication. Caucasian genotypes were combined with the publically-available Framingham Heart Study (FHS; 67 cases, 4712 controls) and Atherosclerosis Risk in Communities Study (ARIC; 153 cases, 6969 controls), with exclusion of cases taking diuretics with gout ascertained by self-report and use of gout medication for FHS and self-report for ARIC. Three PDZK1 variants (rs11576685, rs1284300, rs1967017) were genotyped using Taqman. The variants were tested for association using the Mantel-Haenszel method of meta-analysis.

Results:

All variants were significantly associated with gout: rs11576685, OR = 0.53 [0.34–0.82], P= 0.004; rs1284300, OR = 0.74 [0.59–0.93]. P= 0.009; rs1967017, OR = 1.23 [1.09–1.40], P= 0.001. There was no evidence for heterogeneity – all Breslow-Day P values were greater than 0.09.

Conclusion:

The direction of association with gout of rs1967017 is consistent with that previously reported for control of serum urate levels. None of the variants exhibit any intermarker linkage disequilibrium, implying the existence of multiple gout risk variants within the PDZK1 locus. These results suggest that PDZK1 not only influences metabolic traits and serum urate levels, but also gout.

To cite this abstract, please use the following information:
Merriman, Tony R., Dalbeth, Nicola, Hollis-Moffatt, Jade E., Phipps-Green, Amanda, Topless, Ruth, Merriman, Marilyn E., et al; Association with Gout of PDZK1 Variants That Influence Metabolic Traits and Serum Urate Levels. [abstract]. Arthritis Rheum 2011;63 Suppl 10 :212
DOI:

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