LRP5 基因多态性与类风湿关节炎患者的放射学关节损伤。
LRP5 gene polymorphisms and radiographic joint damage in rheumatoid arthritis patients.
机构信息
Department of Rheumatology, São João Hospital Centre, Porto, Portugal.
Department of Medicine, Faculty of Medicine, University of Porto, Porto, Portugal.
出版信息
Osteoporos Int. 2018 Oct;29(10):2355-2368. doi: 10.1007/s00198-018-4625-3. Epub 2018 Jul 17.
UNLABELLED
Rheumatoid arthritis (RA) is characterized by increased bone resorption and impaired bone formation. Osteoblast function is regulated by the canonical LRP5/Wnt/β-catenin pathway. Bone mineral density and RA joint destruction are partially inherited. In line with this, we found significant associations between LRP5 SNPs (p.A1330V, p.N740N, p.V667M) and RA radiographic damage severity.
INTRODUCTION
Increased bone resorption and impaired bone formation characterize rheumatoid arthritis (RA). Canonical Wnt/β-catenin pathway, signalled by lipoprotein receptor-related protein-5 (LRP5), regulates osteoblast function. Since bone mineral density (BMD) and RA joint destruction are partially inherited, we studied their association with LRP5 single nucleotide polymorphisms (SNPs).
METHODS
Clinical data and peripheral blood for biomarkers assessment and LRP5 genotyping were collected from 208 RA patients. Hands and feet X-rays were scored [modified Sharp/van der Heijde Score (SHS), joint space narrowing (JSN), and erosion scores]. Lumbar spine, total left proximal femur, and left hand BMD were assessed by dual-energy X-ray absorptiometry (DXA).
RESULTS
TT genotypes for p.A1330V and p.N740N LRP5 SNPs associated with total SHS, erosion score, and hands erosion score; the same for p.A1330V with feet JSN score and p.N740N with hands total score. AG genotype for p.V667M associated with sclerostin and hands JSN score. Femoral BMD associated with TC genotype for p.N740N. Multiple test correction precluded a few of these associations. Among V667M-N740N-A1330V haplotypes: GTT associated with higher feet JSN score (OR = 3.80; p = 0.016) and ATT with higher JSN score (OR = 4.60; p = 0.032), hands total score (OR = 5.65; p = 0.022), and total SHS (OR = 6.74; p = 0.024).
CONCLUSION
Significant associations between LRP5 SNPs (p.A1330V, p.N740N, and p.V667M) and the severity of radiographic damage reinforce the evidence of bone destruction heritability in RA.
目的
类风湿关节炎（RA）的特征是骨吸收增加和骨形成受损。成骨细胞功能受经典 LRP5/Wnt/β-连环蛋白通路调控。骨密度和 RA 关节破坏部分具有遗传性。与此一致的是，我们发现 LRP5 单核苷酸多态性（SNP）（p.A1330V、p.N740N、p.V667M）与 RA 放射学损伤严重程度之间存在显著关联。
背景
骨吸收增加和骨形成受损是类风湿关节炎（RA）的特征。由脂蛋白受体相关蛋白 5（LRP5）信号传导的经典 Wnt/β-连环蛋白通路调节成骨细胞功能。由于骨密度（BMD）和 RA 关节破坏部分具有遗传性，因此我们研究了它们与 LRP5 单核苷酸多态性（SNP）的关系。
方法
从 208 例 RA 患者中收集临床数据和用于生物标志物评估和 LRP5 基因分型的外周血。手部和足部 X 射线按改良 Sharp/van der Heijde 评分（SHS）、关节间隙狭窄（JSN）和侵蚀评分进行评分。腰椎、总左侧近端股骨和左手的骨密度通过双能 X 射线吸收法（DXA）评估。
结果
LRP5 SNP p.A1330V 和 p.N740N 的 TT 基因型与总 SHS、侵蚀评分和手部侵蚀评分相关；p.A1330V 与足部 JSN 评分和 p.N740N 与手部总分相关。p.V667M 的 AG 基因型与骨硬化蛋白和手部 JSN 评分相关。股骨 BMD 与 p.N740N 的 TC 基因型相关。多重检验校正排除了其中一些关联。在 V667M-N740N-A1330V 单倍型中：GTT 与较高的足部 JSN 评分相关（OR=3.80；p=0.016），ATT 与较高的 JSN 评分相关（OR=4.60；p=0.032）、手部总分（OR=5.65；p=0.022）和总 SHS（OR=6.74；p=0.024）。
结论
LRP5 SNP（p.A1330V、p.N740N 和 p.V667M）与放射学损伤严重程度之间的显著关联，加强了 RA 中骨破坏遗传性的证据。
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