欧洲和波利尼西亚痛风男性患者中痛风多基因风险评分与疾病发病年龄及痛风石性疾病的关联

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

作者信息

Sumpter Nicholas A, Takei Riku, Cadzow Murray, Topless Ruth K G, Phipps-Green Amanda J, Murphy Rinki, de Zoysa Janak, Watson Huti, Qasim Muhammad, Lupi Alexa S, Abhishek Abhishek, Andrés Mariano, Crișan Tania O, Doherty Michael, Jacobsson Lennart, Janssen Matthijs, Jansen Tim L, Joosten Leo A B, Kapetanovic Meliha, Lioté Frédéric, Matsuo Hirotaka, McCarthy Geraldine M, Perez-Ruiz Fernando, Riches Philip, Richette Pascal, Roddy Edward, Stiburkova Blanka, So Alexander, Tausche Anne-Kathrin, Torres Rosa J, Uhlig Till, Major Tanya J, Stamp Lisa K, Dalbeth Nicola, Choi Hyon K, Vazquez Ana I, Leask Megan P, Reynolds Richard J, Merriman Tony R

机构信息

Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham, and Department of Biochemistry, University of Otago, Dunedin, New Zealand.

Division of Clinical Immunology and Rheumatology, Department of Medicine, University of Alabama at Birmingham.

出版信息

Arthritis Rheumatol. 2023 May;75(5):816-825. doi: 10.1002/art.42393. Epub 2023 Mar 25.

DOI:10.1002/art.42393

PMID:36281732

Abstract

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 (β = -3.61 in years per unit PRS [95% confidence interval (95% CI) -4.32, -2.90] in European men; β = -6.35 [95% CI -8.91, -3.80] in East Polynesian men; β = -3.51 [95% CI -5.46, -1.57] in West Polynesian men) but not in women (β = 0.07 [95% CI -2.32, 2.45] in European women; β = 0.20 [95% CI -7.21, 7.62] in East Polynesian women; β -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 (β = -2.42 [95% CI -3.37, -1.46] and β = -6.80 [95% CI -10.06, -3.55], respectively) but not in West Polynesian men (β = -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.

摘要

目的

确定痛风多基因风险评分（PRS）是否与欧洲、东波利尼西亚和西波利尼西亚痛风患者的痛风发病年龄及痛风石疾病相关。

方法

在7个欧洲痛风队列（N = 4016）、2个东波利尼西亚痛风队列（N = 682）和1个西波利尼西亚痛风队列（N = 490）中生成了一个包含19个变异的痛风PRS。采用性别分层回归模型来估计PRS与痛风发病年龄及痛风石疾病之间的关系。

结果

PRS与男性痛风发病年龄较早相关（欧洲男性中每单位PRS对应的发病年龄变化β = -3.61岁[95%置信区间（95%CI）-4.32，-2.90]；东波利尼西亚男性中β = -6.35[95%CI -8.91，-3.80]；西波利尼西亚男性中β = -3.51[95%CI -5.46，-1.57]），但与女性无关（欧洲女性中β = 0.07[95%CI -2.32，2.45]；东波利尼西亚女性中β = 0.20[95%CI -7.21，7.62]；西波利尼西亚女性中β = -3.33[95%CI -9.28，2.62]）。PRS与男性痛风石疾病呈正相关（欧洲男性中关联的比值比[OR]为1.15[95%CI 1.00，1.31]；东波利尼西亚男性中OR为2.60[95%CI 1.66，4.06]；西波利尼西亚男性中OR为1.53[95%CI 1.07，2.19]），但与女性无关（欧洲女性中关联的OR为0.68[95%CI 0.42，1.10]；东波利尼西亚女性中OR为1.45[95%CI 0.39，5.36]）。在欧洲和东波利尼西亚男性中，去除PRS中的ABCG2变异后，PRS与痛风发病年龄的关联依然稳健（分别为β = -2.42[95%CI -3.37，-1.46]和β = -6.80[95%CI -10.06，-3.55]），但在西波利尼西亚男性中并非如此（β = -1.79[95%CI -4.74，1.16]）。