Open Access Research article

Association of the lipoprotein receptor-related protein 2 gene with gout and non-additive interaction with alcohol consumption

Humaira Rasheed1, Amanda Phipps-Green1, Ruth Topless1, Jade E Hollis-Moffatt1, Jennie Harré Hindmarsh2, Christopher Franklin3, Nicola Dalbeth3, Peter B Jones3, Douglas HN White4, Lisa K Stamp5 and Tony R Merriman1*

Author Affiliations

1 Department of Biochemistry, University of Otago, Dunedin, New Zealand

2 Ngati Porou Hauora Charitable Trust, Te Puia Springs, New Zealand

3 Department of Medicine, University of Auckland, Auckland, New Zealand

4 Department of Rheumatology, Waikato Hospital, Hamilton, New Zealand

5 Department of Medicine, University of Otago, Christchurch, New Zealand

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Arthritis Research & Therapy 2013, 15:R177  doi:10.1186/ar4366

Published: 4 November 2013

Abstract

Introduction

The T allele of a single nucleotide polymorphism (SNP: rs2544390) in lipoprotein receptor-related protein 2 (LRP2) is associated with higher serum urate and risk of gout in Japanese individuals. SNP rs2544390 also interacts with alcohol consumption in determining hyperuricemia in this population. We investigated the association of rs2544390 with gout, and interaction with all types of alcohol consumption in European and New Zealand (NZ) Māori and Pacific subjects, and a Māori study cohort from the East Coast region of NZ’s North Island.

Methods

Rs2544390 was genotyped by Taqman®. From NZ a total of 1205 controls and 1431 gout cases clinically ascertained were used. Publicly available genotype and serum urate data were utilized from the Atherosclerosis Risk in Communities (ARIC) study and the Framingham Heart Study (FHS). Alcohol consumption data were obtained by consumption frequency questions in all study cohorts. Multivariate adjusted logistic regression was done using STATA.

Results

The T allele of rs2544390 was associated with increased risk of gout in the combined Māori and Pacific Island cohort (OR = 1.20, P = 0.009), and associated with gout in the European subjects, but with a protective effect (OR = 0.79, PUnadjusted = 0.02). Alcohol consumption was positively associated with risk of gout in Māori and Pacific subjects (0.2% increased risk/g/week, P = 0.004). There was a non-additive interaction between any alcohol intake and the risk of gout in the combined Māori and Pacific cohorts (PInteraction = 0.001), where any alcohol intake was associated with a 4.18-fold increased risk in the CC genotype group (P = 6.6x10-5), compared with a 1.14-fold increased risk in the CT/TT genotype group (P = 0.40). These effects were not observed in European subjects.

Conclusions

Association of the T-allele with gout risk in the Māori and Pacific subjects was consistent with this allele increasing serum urate in Japanese individuals. The non-additive interaction in the Māori and Pacific subjects showed that alcohol consumption over-rides any protective effect conferred by the CC genotype. Further exploration of the mechanism underlying this interaction should generate new understanding of the biological role of alcohol in gout, in addition to strengthening the evidence base for reduction of alcohol consumption in the management of gout.