刺猬信号基因HHIP启动子区甲基化与汉族老年骨质疏松症的相关性  

Relationship between methylation of Hedgehog signal gene HHIP promoter region and osteoporosis in elderly Han people

作　　者：卓娅·买买提乌斯满[1] 塔吉古丽·木沙[1] 王红梅[1] ZOYA Maimattiusman;TAGUIGUL Musha;WANG Hongmei(Department of the Second Cadre Health, Xinjiang Uygur Autonomous Region People's Hospital, Urumqi 830002, China)

机构地区：[1]新疆维吾尔自治区人民医院干部保健二科,新疆乌鲁木齐830002

出　　处：《西部医学》2021年第8期1159-1164,共6页Medical Journal of West China

基　　金：国家自然科学基金(81660242)。

摘　　要：目的探讨老年骨质疏松症患者外周血中Hedgehog相互作用蛋白(HHIP)的启动子区甲基化。方法选取2017年7月~2019年7月我院收治的102例汉族老年性骨质疏松症(SOP)患者为观察组,并选取同期于我院体检中心体检的100例汉族老年健康者为对照组。检测两组患者的血清骨代谢标记物I型前胶原氨基端肽(P1NP)和β-骨原交联(β-CrossLaps)的水平以及血钙含量;分离两组患者外周血单个核细胞,荧光定量PCR检测HHIP、SHH、PTCH1、SMO、Gli1和Gli2的mRNA表达量;使用甲基化酶法检测单个核细胞中目标基因的启动子区甲基化状态,实时荧光定量RTqPCR检测目标基因表达。分析以上指标之间的相关性。结果观察组SHH、PTCH1、SMO和Gli mRNA在单个核细胞中下调,而HHIP的mRNA在单个核细胞中上调约4倍(均P<0.05)。观察组中HHIP基因启动子区甲基化水平显著低于对照组(P<0.05)。观察组的血钙低于对照组,而血清P1NP和β-CrossLaps显著高于对照组(均P<0.05)。HHIP启动子区的甲基化水平与P1NP和β-CrossLaps呈负相关(均P<0.05)。结论外周血单个核细胞中刺猬信号基因的表达和HHIP的甲基化水平在汉族老年骨质疏松症诊断中具有一定价值,其水平与骨代谢异常具有相关性。Objective To study the methylation of Hedgehog interacting protein(HHIP)promoter region in peripheral blood in elderly patients with osteoporosis.Methods 102 cases of senile osteoporosis(SOP)patients in our hospital from July 2017 to July 2019 were selected as the observation group,and 100 cases of healthy elderly people in our hospital physical examination center were selected as the control group.The serum levels of bone metabolism markers,Ⅰ-type procollagen N-terminal peptide(p1np)and insulin resistance were detectedβOsteogenic crosslinking(βThe level of cross laps and blood calcium content were measured;The mRNA expressions of HHIP,Shh,PTCH1,SMO,Gli1 and Gli2 were detected by real-time PCR.The methylation status of the promoter region of the target gene in mononuclear cells was detected by methylase method,and the expression of the target gene was detected by real-time fluorescent quantitative RT qPCR.Analyze the correlation between the above indicators.Results SHH,PTCH1,SMO and Gli mRNA were down-regulated in the mononuclear cells of the observation group(all P<0.05).The HHIP mRNA was up-regulated about 4 times in the mononuclear cells of the observation group(P<0.01).The methylation level of HHIP gene promoter region in the observation group was significantly lower than that in the control group(P<0.05).The blood calcium in the observation group was lower than that in the control group(P<0.05),while the serum P1NP(P<0.05)andβ-CrossLaps(P<0.05)were significantly higher than those in the control group.The methylation level of the HHIP promoter region was negatively correlated with P1NP andβ-CrossLaps,with statistical significance(both P<0.05).Conclusion The expression of Hedgehog signaling gene in peripheral blood mononuclear cells and the methylation level of HHIP have certain value in the diagnosis of osteoporosis in the elderly,its level is related to abnormal bone metabolism.

关 键 词：HHIP 启动子区 甲基化 汉族老年人 骨质疏松症 

分 类 号：R681[医药卫生—骨科学]