Replication of association of the apolipoprotein A1-C3-A4 gene cluster with the risk of gout.
Gout is associated with dyslipidaemia. Association of the apolipoprotein A1-C3-A4 gene cluster with gout has previously been reported in a small study. To investigate a possible causal role for this locus in gout, we tested the association of genetic variants from APOA1 (rs670) and APOC3 (rs5128) with gout.



We studied data for 2452 controls and 2690 clinically ascertained gout cases of European and New Zealand Polynesian (Māori and Pacific) ancestry. Data were also used from the publicly available Atherosclerosis Risk in Communities study (n = 5367) and the Framingham Heart Study (n = 2984). Multivariate adjusted logistic and linear regression was used to test the association of single-nucleotide polymorphisms with gout risk, serum urate, triglyceride and high-density lipoprotein cholesterol (HDL-C).



In Polynesians, the T-allele of rs670 (APOA1) increased (odds ratio, OR = 1.53, P = 4.9 × 10(-6)) and the G-allele of rs5128 (APOC3) decreased the risk of gout (OR = 0.86, P = 0.026). In Europeans, there was a strong trend to a risk effect of the T-allele for rs670 (OR = 1.11, P = 0.055), with a significant protective effect of the G-allele for rs5128 being observed after adjustment for triglycerides and HDL-C (OR = 0.81, P = 0.039). The effect at rs5128 was specific to males in both Europeans and Polynesians. Association in Polynesians was independent of any effect of rs670 and rs5128 on triglyceride and HDL-C levels. There was no evidence for association of either single-nucleotide polymorphism with serum urate levels (P ⩾ 0.10).



Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.
Department of Biochemistry, University of Otago, Dunedin, New Zealand Department of Chemistry, University of Engineering and Technology, Lahore, Pakistan.
Humaira
H
Rasheed
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Amanda J
AJ
Phipps-Green
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Ruth
R
Topless
Department of Medicine, Flinders Medical Centre and Repatriation General Hospital, Adelaide.
Malcolm D
MD
Smith
Rheumatology Department, The Queen Elizabeth Hospital, Woodville South, SA, Australia.
Catherine
C
Hill
Rheumatology Department, The Queen Elizabeth Hospital, Woodville South, SA, Australia.
Susan
S
Lester
Rheumatology Department, The Queen Elizabeth Hospital, Woodville South, SA, Australia.
Maureen
M
Rischmueller
Department of Rheumatology, Rijnstate Hospital, Arnhem.
Matthijs
M
Janssen
Department of IQ HealthCare, VieCuri Medical Centre, Venlo.
Timothy L
TL
Jansen
Department of Internal Medicine and Radboud Institute of Molecular Life Science, Radboud University Medical Center, Nijmegen.
Leo A
LA
Joosten
Department of Rheumatology and Clinical Immunology, Laboratory of Translational Immunology, University Medical Centre Utrecht, Utrecht, The Netherlands.
Timothy R
TR
Radstake
Rheumatic Diseases Unit, Institute of Genetics and Molecular Medicine, University of Edinburgh, Edinburgh, UK.
Philip L
PL
Riches
Department of Rheumatology, University Clinic Carl-Gustav-Carus, Dresden, Germany.
Anne-Kathrin
AK
Tausche
INSERM, UMR-S 1132, Hospital Lariboisière University Paris Diderot (UFR de Médecine), Sorbonne Paris Cité, Paris, F-75205, France.
Frederic
F
Lioté
DAL, Service of Rheumatology, Laboratory of Rheumatology, University of Lausanne, CHUV, Nestlé 05-5029, Lausanne, Switzerland.
Alexander
A
So
Department of Surgery, University of Otago, Dunedin.
Andre
A
van Rij
Department of Surgery, University of Otago, Dunedin.
Gregory T
GT
Jones
Department of Biochemistry, University of Otago, Dunedin, New Zealand.
Sally P
SP
McCormick
Department of Medicine, University of Otago, Wellington.
Andrew A
AA
Harrison
Department of Medicine, University of Otago, Christchurch.
Lisa K
LK
Stamp
Department of Medicine, University of Auckland, Auckland, New Zealand.
Nicola
N
Dalbeth
Department of Biochemistry, University of Otago, Dunedin, New Zealand tony.merriman@otago.ac.nz.
Tony R
TR
Merriman
D000328:Adult; D016632:Apolipoprotein A-I / Q000235:genetics*; D053305:Apolipoprotein C-III / Q000235:genetics; D001056:Apolipoproteins C / Q000235:genetics; D016022:Case-Control Studies; D005260:Female; D005838:Genotype; D006073:Gout / Q000235:genetics*; D006801:Humans; D008297:Male; D008875:Middle Aged; D005810:Multigene Family / Q000235:genetics*; D012307:Risk Factors; D014527:Uric Acid / Q000378:metabolism; D044465:White People / Q000235:genetics
C505693:APOA1 protein, human; C097349:APOC4 protein, human; D016632:Apolipoprotein A-I; D053305:Apolipoprotein C-III; D001056:Apolipoproteins C; D014527:Uric Acid
apolipoprotein; association; gene; gout; hyperuricaemia