The effect of systemic iron status on osteoarthritis: A mendelian randomization study

被引:7
|
作者
Ruan, Guangfeng [1 ]
Ying, Yi [2 ]
Lu, Shilong [3 ]
Zhu, Zhaohua [4 ]
Chen, Shibo [4 ]
Zeng, Muhui [4 ]
Lu, Ming [5 ]
Xue, Song [6 ]
Zhu, Jianwei [7 ]
Cao, Peihua [4 ]
Chen, Tianyu [4 ]
Wang, Xiaoshuai [4 ]
Li, Shengfa [4 ]
Li, Jia [4 ]
Liu, Yu [4 ]
Liu, Yanqi [4 ]
Zhang, Yan [4 ]
Ding, Changhai [1 ,4 ,8 ]
机构
[1] South China Univ Technol, Guangzhou Peoples Hosp 1, Clin Res Ctr, Sch Med, Guangzhou, Peoples R China
[2] South China Univ Technol, Guangzhou Peoples Hosp 1, Sch Med, Dept Hematopathol, Guangzhou, Peoples R China
[3] Southern Med Univ, Zhujiang Hosp, Dept Imaging Diag, Guangzhou, Peoples R China
[4] Southern Med Univ, Zhujiang Hosp, Clin Res Ctr, Guangzhou, Peoples R China
[5] Anhui Med Univ, Sch Basic Med Sci, Dept Immunol, Hefei, Peoples R China
[6] Anhui Med Univ, Affiliated Hosp 1, Arthrit Res Inst, Dept Rheumatol & Immunol, Hefei, Peoples R China
[7] South China Univ Technol, Guangzhou Peoples Hosp 1, Sch Med, Dept Orthoped, Guangzhou, Peoples R China
[8] Univ Tasmania, Menzies Inst Med Res, Hobart, Tas, Australia
基金
中国国家自然科学基金;
关键词
iron; rs1800562; hip osteoarthritis (hip OA); total hip replacement (THR); mendelian randomization (MR); MULTIPLE GENETIC-VARIANTS; KNEE OSTEOARTHRITIS; CAUSAL INFERENCE; HEMOCHROMATOSIS; HOMEOSTASIS; METABOLISM; OVERLOAD; COPPER; JOINT; RISK;
D O I
10.3389/fgene.2023.1122955
中图分类号
Q3 [遗传学];
学科分类号
071007 ; 090102 ;
摘要
Objective: To assess the causal effect of systemic iron status by using four biomarkers (serum iron; transferrin saturation; ferritin; total iron-binding capacity) on knee osteoarthritis (OA), hip OA, total knee replacement, and total hip replacement using 2-sample Mendelian randomization (MR) design.Methods: Three instrument sets were used to construct the genetic instruments for the iron status: Liberal instruments (variants associated with one of the iron biomarkers), sensitivity instruments (liberal instruments exclude variants associated with potential confounders), and conservative instruments (variants associated with all four iron biomarkers). Summary-level data for four OA phenotypes, including knee OA, hip OA, total knee replacement, and total hip replacement were obtained from the largest genome-wide meta-analysis with 826,690 individuals. Inverse-variance weighted based on the random-effect model as the main approach was conducted. Weighted median, MR-Egger, and Mendelian randomization pleiotropy residual sum and outlier methods were used as sensitivity MR approaches.Results: Based on liberal instruments, genetically predicted serum iron and transferrin saturation were significantly associated with hip OA and total hip replacement, but not with knee OA and total knee replacement. Statistical evidence of heterogeneity across the MR estimates indicated that mutation rs1800562 was the SNP significantly associated with hip OA in serum iron (odds ratio, OR = 1.48), transferrin saturation (OR = 1.57), ferritin (OR = 2.24), and total-iron binding capacity (OR = 0.79), and hip replacement in serum iron (OR = 1.45), transferrin saturation (OR = 1.25), ferritin (OR = 1.37), and total-iron binding capacity (OR = 0.80).Conclusion: Our study suggests that high iron status might be a causal factor of hip OA and total hip replacement where rs1800562 is the main contributor.
引用
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页数:12
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