Association of Gout Polygenic Risk Score With Age at Disease Onset and Tophaceous Disease in European and Polynesian Men With Gout

被引：12

作者：

Sumpter, Nicholas A. ^{[1
,2
]}

Takei, Riku ^{[1
]}

Cadzow, Murray ^{[2
]}

Topless, Ruth K. G. ^{[2
]}

Phipps-Green, Amanda J. ^{[2
]}

Murphy, Rinki ^{[3
]}

de Zoysa, Janak ^{[3
]}

Watson, Huti ^{[4
]}

Qasim, Muhammad ^{[4
]}

Lupi, Alexa S. ^{[5
,6
]}

Abhishek, Abhishek ^{[7
]}

Andres, Mariano ^{[8
,9
,10
]}

Crisan, Tania O. ^{[11
,12
]}

Doherty, Michael ^{[7
]}

Jacobsson, Lennart ^{[13
,14
]}

Janssen, Matthijs

Jansen, Tim L. ^{[15
,16
]}

Joosten, Leo A. B. ^{[17
,18
,19
]}

Kapetanovic, Meliha ^{[20
,21
,22
]}

Liote, Frederic ^{[23
,24
,25
,26
]}

Matsuo, Hirotaka ^{[27
,28
]}

McCarthy, Geraldine M. ^{[29
,30
,31
]}

Perez-Ruiz, Fernando ^{[32
,33
,34
,35
]}

Riches, Philip ^{[36
,37
]}

Richette, Pascal ^{[23
,24
,25
,26
]}

Roddy, Edward ^{[38
,39
]}

Stiburkova, Blanka ^{[40
,41
,42
,43
]}

So, Alexander ^{[44
,45
,46
]}

Tausche, Anne-Kathrin ^{[47
,48
]}

Torres, Rosa J. ^{[49
,50
,51
]}

Uhlig, Till ^{[52
,53
,54
]}

Major, Tanya J. ^{[2
]}

Stamp, Lisa K. ^{[55
,56
]}

Dalbeth, Nicola ^{[57
,58
]}

Choi, Hyon K.

Vazquez, Ana I. ^{[5
,6
]}

Leask, Megan P. ^{[1
]}

Reynolds, Richard J. ^{[1
]}

Merriman, Tony R. ^{[1
,2
,59
,60
]}

机构：

[1] Univ Alabama Birmingham, Dept Med, Div Clin Immunol & Rheumatol, Birmingham, AL 35205 USA

[2] Univ Otago, Dept Biochem, Dunedin, New Zealand

[3] Univ Auckland, Fac Med & Hlth Sci, Dept Med, Auckland, New Zealand

[4] Ngati Porou Hauora Trust, Te Puia Springs, New Zealand

[5] Michigan State Univ, Dept Epidemiol & Biostat, E Lansing, MI USA

[6] Michigan State Univ, Inst Quantitat Hlth Sci & Engn, E Lansing, MI USA

[7] Univ Nottingham, Nottingham City Hosp, Sch Med, Acad Rheumatol, Nottingham, England

[8] GlobalGoutGenet Consortium, Nottingham, England

[9] GlobalGoutGenet Consortium, Alicante, Spain

[10] Miguel Hernandez Univ, Alicante Gen Univ Hosp, Dept Rheumatol, ISA,BIAL, Alicante, Spain

[11] GlobalGoutGenet Consortium, Cluj Napoca, Romania

[12] Iuliu Hatieganu Univ Med & Pharm, Dept Med Genet, Cluj Napoca, Romania

[13] GlobalGoutGenet Consortium, Gothenburg, Sweden

[14] Univ Gothenburg, Inst Med, Sahlgrenska Acad, Dept Rheumatol & Inflammat Res, Gothenburg, Sweden

[15] GlobalGoutGenet Consortium, Venlo, Netherlands

[16] Viecuri Med Ctr, Complex Gout Expert Ctr, Dept Rheumatol, Venlo, Netherlands

[17] GlobalGoutGenet Consortium, Cluj Napoca, Romania

[18] Iuliu Hatieganu Univ Med & Pharm, Dept Med Genet, Cluj Napoca, Romania

[19] Radboud Univ Nijmegen Med Ctr, Radboud Inst Mol Life Sci RIMLS, Dept Internal Med, Nijmegen, Netherlands

[20] GlobalGoutGenet Consortium, Lund, Sweden

[21] Lund Univ, Lund, Sweden

[22] Skane Univ Hosp, Lund, Sweden

[23] GlobalGoutGenet Consortium, Paris, France

[24] Hop Lariboisiere, Assistance Publ Hop Paris, Paris, France

[25] INSERM UMR 1132, Paris, France

[26] Univ Paris Cite, Paris, France

[27] GlobalGoutGenet Consortium, Saitama, Japan

[28] Natl Def Med Coll, Dept Integrat Physiol & Bionano Med, Saitama, Japan

[29] GlobalGoutGenet Consortium, Dublin, Ireland

[30] Mater Misericordiae Univ Hosp, Dublin, Ireland

[31] Univ Coll, Dublin, Ireland

[32] GlobalGoutGenet Consortium, Baracaldo, Spain

[33] Cruces Univ Hosp, OSI EE Cruces, Div Rheumatol, Baracaldo, Spain

[34] Biocruces Bizkaia Hlth Res Inst, Baracaldo, Spain

[35] Univ Basque Country, Med Sch, Med Dept, Leioa, Spain

[36] GlobalGoutGenet Consortium, Edinburgh, Scotland

[37] Univ Edinburgh, IGC, Edinburgh, Scotland

[38] GlobalGoutGenet Consortium, Keele, Staffs, England

[39] Keele Univ, Sch Med, Keele, Staffs, England

[40] GlobalGoutGenet Consortium, Prague, Czech Republic

[41] Charles Univ Prague, Fac Med 1, Dept Pediat & Inherited Metab Disorders, Prague, Czech Republic

[42] Gen Univ Hosp, Prague, Czech Republic

[43] Inst Rheumatol, Prague, Czech Republic

[44] GlobalGoutGenet Consortium, Lausanne, Switzerland

[45] CHU Vaudois, Dept Musculoskeletal Med, Serv Rheumatol, Lausanne, Switzerland

[46] Univ Lausanne, Lausanne, Switzerland

[47] GlobalGoutGenet Consortium, Dresden, Germany

[48] Tech Univ Dresden, Univ Clin Carl Gustav Carus, Div Rheumatol, Dresden, Germany

[49] GlobalGoutGenet Consortium, Madrid, Spain

[50] La Paz Univ Hosp Hlth Res Inst FIBHULP, Dept Biochem, IdiPaz, Madrid, Spain

来源：

ARTHRITIS & RHEUMATOLOGY | 2023年 / 75卷 / 05期

关键词：

LESINURAD; EPIDEMIOLOGY; ALLOPURINOL; DEFINITION; INHIBITOR; FLARE;

D O I：

10.1002/art.42393

中图分类号：

R5 [内科学];

学科分类号：

1002 ; 100201 ;

摘要：

Objective. To determine whether a gout polygenic risk score (PRS) is associated with age at gout onset and tophaceous disease in European, East Polynesian, and West Polynesian men and women with gout. Methods. A 19-variant gout PRS was produced in 7 European gout cohorts (N = 4,016), 2 East Polynesian gout cohorts (N = 682), and 1 West Polynesian gout cohort (N = 490). Sex-stratified regression models were used to estimate the relationship between the PRS and age at gout onset and tophaceous disease. Results. The PRS was associated with earlier age at gout onset in men (beta = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; beta = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; beta = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (beta = 0.07 [95% CI -2.32, 2.45] in European women; beta = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; beta -3.33 [95% CI -9.28, 2.62] in West Polynesian women). The PRS showed a positive association with tophaceous disease in men (odds ratio [OR] for the association 1.15 [95% CI 1.00, 1.31] in European men; OR 2.60 [95% CI 1.66, 4.06] in East Polynesian men; OR 1.53 [95% CI 1.07, 2.19] in West Polynesian men) but not in women (OR for the association 0.68 [95% CI 0.42, 1.10] in European women; OR 1.45 [95% CI 0.39, 5.36] in East Polynesian women). The PRS association with age at gout onset was robust to the removal of ABCG2 variants from the PRS in European and East Polynesian men (beta = -2.42 [95% CI -3.37, -1.46] and beta = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (beta = -1.79 [95% CI -4.74, 1.16]). Conclusion. Genetic risk variants for gout also harbor risk for earlier age at gout onset and tophaceous disease in European and Polynesian men. Our findings suggest that earlier gout onset involves the accumulation of gout risk alleles in men but perhaps not in women, and that this genetic risk is shared across multiple ancestral groups.

引用

页码：816 / 825

页数：10

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