TY - JOUR
T1 - Replication of association of the apolipoprotein A1-C3-A4 gene cluster with the risk of gout
AU - Rasheed, Humaira
AU - Phipps-Green, Amanda J.
AU - Topless, Ruth
AU - Smith, Malcolm D.
AU - Hill, Catherine
AU - Lester, Susan
AU - Rischmueller, Maureen
AU - Janssen, Matthijs
AU - Jansen, Timothy L.
AU - Joosten, Leo A.
AU - Radstake, Timothy R.
AU - Riches, Philip L.
AU - Tausche, Anne Kathrin
AU - Lioté, Frederic
AU - So, Alexander
AU - Van Rij, Andre
AU - Jones, Gregory T.
AU - McCormick, Sally P.
AU - Harrison, Andrew A.
AU - Stamp, Lisa K.
AU - Dalbeth, Nicola
AU - Merriman, Tony R.
PY - 2016/8/1
Y1 - 2016/8/1
N2 - Objective. 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. Methods. 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). Results. 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). Conclusion. Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.
AB - Objective. 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. Methods. 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). Results. 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). Conclusion. Our data, replicating a previous study, supports the hypothesis that the apolipoprotein A1-C3-A4 gene cluster plays a causal role in gout.
KW - Apolipoprotein
KW - Association
KW - Gene
KW - Gout
KW - Hyperuricaemia
UR - http://www.scopus.com/inward/record.url?scp=84988632767&partnerID=8YFLogxK
U2 - 10.1093/rheumatology/kew057
DO - 10.1093/rheumatology/kew057
M3 - Article
C2 - 27094595
AN - SCOPUS:84988632767
SN - 1462-0324
VL - 55
SP - 1421
EP - 1430
JO - Rheumatology (Oxford, England)
JF - Rheumatology (Oxford, England)
IS - 8
ER -