摘要
目的研究中国X-连锁显性低血磷性佝偻病/骨软化症(X-linked dominant hypophosphatemic rickets/osteomalacia,XLH)患者血清成纤维细胞生长因子23 (fibroblast growth factor-23,FGF-23)水平特征,以及其与患者基因突变型及疾病表型严重程度的相关性。方法收集2005至2017年就诊于北京协和医院内分泌科的XLH患者233例,所有患者均已明确致病突变。收集患者初次就诊血清,采用双抗夹心酶联免疫吸附法Elisa试剂盒进行i FGF-23水平测定。分析全段FGF-23 (intact FGF-23,i FGF-23)水平在不同性别患者中的差异,及其与致病基因PHEX突变类型/位置和疾病严重程度的相关性。结果 233例XLH患者均行i FGF-23测定,患者整体i FGF-23中位水平为101. 9 (71. 37,143. 81) ng/L,较正常参考范围(16. 1～42. 2 ng/L)显著升高,但XLH患者i FGF-23水平个体差异很大(6. 46～542. 57 ng/L)。XLH患者i FGF-23水平性别差异无统计学意义(P=0. 668),且与患者年龄亦无显著相关性(r=-0. 082,P=0. 254)。i FGF-23水平不受患者PHEX基因突变类型(截短/非截短突变)或突变位置(N端/C端突变,锌离子结合域/非锌离子结合域)的影响,差异均无统计学意义(P>0. 05)。i FGF-23与患者疾病临床表型严重程度[起病年龄、血磷/正常上限比、身高(SD值)及佝偻病骨骼表现严重程度]亦无显著相关性(P>0. 05)。结论中国XLH患者人群血清i FGF-23水平较正常人群显著升高,但个体差异较大; i FGF-23水平与患者年龄、PHEX基因突变类型或位置、患者疾病严重程度无相关性。i FGF-23可以作为明确诊断XLH疾病的一项重要指标,然而其升高程度并不能预测或代表患者疾病严重程度。
Objective To study the characteristics of serum intact fibroblast growth facter-23(iFGF-23)levels in X-linked hypophosphatemia(XLH)patients,and the correlation between iFGF-23 and genotype or disease severity.Methods We retrospectively recruited 233 XLH patients diagnosed with XLH with specific PHEX mutations.Blood serum was collected from all patients at their first visit to the clinic.Serum iFGF-23 levels were measured using a two-site ELISA kit(KAINOS Laboratories,Japan).We analyzed the correlation between iFGF-23 levels and PHEX mutation types or locations,as well as disease severity of the patients.Results iFGF-23 levels varied widely in our XLH cohort,ranging from 6.46 to 542.57 ng/L,with a median value of 101.9 ng/L.Serum iFGF-23 levels of 91.9% patients were above the upper limit of the reference range.iFGF-23 levels were not affected by either PHEX mutation types or locations.In addition,iFGF-23 had no correlation with disease severity of XLH(P>0.05),including age of onset,serum phosphate/upper limit ratio,height SD values and rickets severity score(RSS).Conclusion iFGF-23 level is significantly elevated,but widely varied,in our large Chinese XLH patients cohort.We found iFGF-23 was not affected by either sex or PHEX mutation types or locations.iFGF-23 is considered to be an important indicator of XLH,nevertheless the increasing degree of iFGF-23 cannot indicate disease severity of XLH.
作者
张丛
赵真
许莉军
庞倩倩
虞凡
姜艳
王鸥
李梅
邢小平
夏维波
ZHANG Cong;ZHAO Zhen;XU Li-jun;PANG Qian-qian;YU Fan;JIANG Yan;WANG Ou;LI Mei;XING Xiao-ping;XIA Wei-bo(Department of Endocrinology,Peking Union Medical College Hospital,Chinese Academy of Medical Sciences & Peking Union Medical College,Key Laboratory of Endocrinology,National Health Commission of the People s Republic of China,Beijing 100730,China)
出处
《中华骨质疏松和骨矿盐疾病杂志》
CSCD
北大核心
2019年第1期24-31,共8页
Chinese Journal Of Osteoporosis And Bone Mineral Research
基金
国家自然科学基金(81670714)
北京自然科学基金(7121012)
北京医学发展科学研究基金(2007-3029)
国家临床科学重点项目(WBYZ2011-873)
中国医学科学院医学与健康科技创新工程项目(2016-I2M-3-003)
