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CN-121978345-A - Hormone femoral head necrosis high risk prediction marker, kit and detection system

CN121978345ACN 121978345 ACN121978345 ACN 121978345ACN-121978345-A

Abstract

The invention relates to a hormonal femoral head necrosis (SONFH) high-risk prediction marker, a kit and a detection system, wherein the markers are ANK1 and EPB41. The invention discovers that ANK1 and EPB41 mutation are closely related to SONFH, can make early warning and prediction through sequencing, screens high-risk individuals, lays a foundation for subsequent development of SONFH prevention (intervention) drugs, and has good application prospect.

Inventors

  • CHEN SHENGBAO
  • ZHANG CHANGQING

Assignees

  • 上海市第六人民医院

Dates

Publication Date
20260505
Application Date
20260107

Claims (8)

  1. 1. A high risk prediction marker for hormonal femoral head necrosis, which is characterized in that the markers are ankyrin-1 ANK1 and erythrocyte membrane protein band 4.1 epb41.
  2. 2. The high risk predictive marker of hormonal femoral head necrosis according to claim 1, wherein said rare variations of ANK1 and EPB41 are closely related to the risk of hormonal femoral head necrosis onset.
  3. 3. The high risk predictive marker of hormonal femoral head necrosis of claim 2, wherein the rare variation comprises one or more of ANK1 p.S1507P、ANK1 p.L1194P、ANK1 p.V991M、ANK1 p.A560T、ANK1 p.V435M、ANK1 p.D1030G、ANK1 p.R941Q、ANK1 p.D11N、EPB41 p.P137L、EPB41 p.P357L、EPB41 p.R700Q.
  4. 4. The high risk predictive marker of hormonal femoral head necrosis according to claim 2, wherein the primer sequence for detecting rare variations is shown in SEQ No. 1-22.
  5. 5. A kit for predicting high risk of hormonal necrosis of femoral head, which is characterized by comprising the primer sequence of claim 4.
  6. 6. The kit for high risk prediction of hormonal femoral head necrosis according to claim 5, wherein the kit further comprises other conventional detection reagents.
  7. 7. A hormonal femoral head necrosis risk prediction system, which is characterized by comprising a peripheral blood smear detection module, a red blood cell hypotonic hemolysis detection module and a sequencing module comprising the kit of claim 5.
  8. 8. The system of claim 7, wherein the peripheral blood smear test module is used for judging whether a dominant or potential abnormal erythrocyte morphological increase exists, the erythrocyte hypotonic hemolysis test module is used for judging whether an erythrocyte membrane fragility increase exists, and the sequencing module is used for confirming whether an invisible erythrocyte membrane defect exists.

Description

Hormone femoral head necrosis high risk prediction marker, kit and detection system Technical Field The invention belongs to the technical field of early warning and prediction of side effects of medicines, and particularly relates to a high-risk prediction marker, a kit and a detection system for hormonal femoral head necrosis. Background Glucocorticoids are an anti-inflammatory and immunosuppressive drug widely used in clinic, and serious adverse reactions occur in some patients in the process of exerting therapeutic effects. Wherein, the hormone femoral head necrosis (Steroid-induced osteonecrosis of the femoral head, SONFH) induced by glucocorticoid (hereinafter referred to as hormone) treatment is a complex refractory skeletal disease, which is one of the most serious complications induced by hormone. SONFH is a disastrous bone disease in pathological mechanism because bone cells are necrotized due to microcirculation disturbance in femoral head blood supply area, limb disability and disability are easy to cause after the disease is generated. The total incidence rate of SONFH is about 3% -40% different in the extensive patient population with different basic diseases requiring hormone treatment, and the total incidence rate of SONFH is estimated to be maintained between 6% -9% by the latest two domestic investigation data (lupus erythematosus patients). And there is a significant difference in hormone tolerance among individuals, the current main academic view considers SONFH onset as a result of the combined action of hormone exposure and individual genetic variation. Common genetic variations and other risk associations of non-coding region variations with SONFH (such variations contribute very little to the risk burden of complex diseases) have been mainly mentioned in terms of individual genetic factors, and there is currently no reported evidence of the association of rare deleterious variations (genetic variations in regions encoding proteins, such variations being generally considered as causative risk factors for complex diseases) with SONFH disease risk. Disclosure of Invention The invention aims to solve the technical problem of providing a high risk prediction marker, a kit and a detection system for hormonal femoral head necrosis, and discovers that ANK1 and EPB41 mutations are closely related to SONFH morbidity, can make high risk individual discrimination, early warning and prediction through sequencing, lays a foundation for subsequent development of SONFH preventive (intervention) medicines, and has good application prospects. In a first aspect, the present invention provides a high risk predictive marker of hormonal femoral head necrosis, said markers being ankyrin-1 (ankyrin-1, ank 1) and erythrocyte membrane protein band 4.1 (erythrocyte membrane protein band.4.1, epb 41). Further, the rare variations of ANK1 and EPB41 are closely related to the risk of hormonal femoral head necrosis onset. Further, the rare variations include one or more of ANK1 p.S1507P、ANK1 p.L1194P、ANK1 p.V991M、ANK1 p.A560T、ANK1 p.V435M、ANK1 p.D1030G、ANK1 p.R941Q、ANK1 p.D11N、EPB41 p.P137L、EPB41 p.P357L、EPB41 p.R700Q. The rare deleterious variants are those in The genome aggregation database (Genome Aggregation Database, gnomAD) and The thousand genome project (The 1000 Genomes Project, 1 kGP), the minor allele frequencies (Minor Allele Frequency, MAF) <0.1% and simultaneously meet The criteria including SIFT prediction as deleterious (deleterious), polyPhen-2 prediction as likely or likely deleterious (probably _ damaging or possibly _ damaging), and CADD score > 20, etc. function prediction as deleterious. Further, the primer sequences for detecting rare variation are shown in SEQ NO. 1-22. In a second aspect, the invention provides a kit for predicting high risk of hormonal femoral head necrosis, which comprises the primer sequence. Further, the kit may also include other conventional detection reagents. In a third aspect, the invention provides a hormonal femoral head necrosis risk prediction system, which comprises a peripheral blood smear detection module, a red blood cell hypotonic hemolysis detection module and a sequencing module of the kit. Further, the peripheral blood smear checking module is used for judging whether an abnormal red blood cell morphology increase exists, such as dominant or potential spherical, oval and the like, the red blood cell hypotonic hemolysis detecting module is used for judging whether an increased fragility of a red blood cell membrane exists, and the sequencing module is used for confirming whether a hidden red blood cell membrane defect exists. In a fourth aspect, the present invention provides a method for early warning and predicting a patient with a risk of hormonal necrosis of the femoral head after hormone therapy, comprising the steps of: (1) For new patients requiring long-term hormone therapy, blood sampling is carried out before hormone therapy is planned, and be