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Methods And Kits For Detecting Risk Factors For Development Of Jaw Osteonecrosis And Methods Of Treatment Thereof

A kit, jawbone technology, applied in the fields of genetics and medicine, molecular biology, can solve problems such as failure to heal, bone exposure, etc.

Inactive Publication Date: 2012-12-05
UNIV OF FLORIDA RES FOUNDATION INC
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  • Summary
  • Abstract
  • Description
  • Claims
  • Application Information

AI Technical Summary

Problems solved by technology

Spontaneous destruction of the overlying mucosa, some forms of injury, or invasive surgery of the jaw often result in this necrotic bone exposure, which has not healed thereafter

Method used

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  • Methods And Kits For Detecting Risk Factors For Development Of Jaw Osteonecrosis And Methods Of Treatment Thereof
  • Methods And Kits For Detecting Risk Factors For Development Of Jaw Osteonecrosis And Methods Of Treatment Thereof
  • Methods And Kits For Detecting Risk Factors For Development Of Jaw Osteonecrosis And Methods Of Treatment Thereof

Examples

Experimental program
Comparison scheme
Effect test

Embodiment 1

[0110] Example 1 - Allele Frequency Determination for SNPs

[0111] method

[0112] Genomic DNA was isolated from lymphocytes in whole blood using a commercially available kit (Qiagen DNA Blood Isolation Kit, Qiagen, Valencia, CA). The isolated DNA samples were quantified and normalized to 20 ng / ul by spectrophotometry and agarose gel electrophoresis.

[0113] by PCR and by fluorescence-based TaqMan (Applied Biosystems, FosterCity, USA) typing method (De la Vega et al. Mutat Res.573 (1-2): 111-135, 2005) for two allelic SNPs, chromosome 17 COL1A1 gene SNP [A / C ], dbSNP ID (rs1800012) (SEQ ID NO: 15) and chromosome 18 TNFRSF11A gene SNP [A / G], dbSNP ID (rs12458117) (SEQ ID NO: 1), for genotyping.

[0114] From Applied Biosystems, Foster City, USA purchase TaqMan genotyping analysis probe [for No. 17 chromosome COL1A1 gene SNP [A / C], the C__7477174_30 of dbSNP ID (rs1800012) (SEQ ID NO: 15), and for 18 Chromosome TNFRSF11A gene SNP [A / G], C___31393804] of dbSNP ID (rs124581...

Embodiment 2

[0120] Example 2 - Genotyping of SNPs

[0121] Genomic DNA was isolated from lymphocytes from blood samples of 50 subjects, 6 BONJ patients and 45 controls (patients without BONJ) and genotyped for 4 single nucleotide polymorphisms (SNPs) : dbSNP ID of CYP2C8 gene (rs1934980) (SEQ ID NO: 13) and rs1934951 (SEQ ID NO: 14)), dbSNP ID of COL1A1 gene (rs1800012) (SEQ ID NO: 15) and dbSNP ID of TNFRSF11A gene (rs12458117 ) (SEQ ID NO: 1).

[0122]

[0123]

Embodiment 3

[0124] Example 3-Analysis of the BONJ Correlation of Candidate Gene SNPs

[0125] Medical and dental charts for the University of Florida (UF) and associated Veterans Administration Medical Centers (VAMCs) were reviewed. As shown in Table 2, 27 patients with BONJ were identified, with a median age of 62 years, 19 with myeloma, 3 with prostate cancer, 2 with breast cancer, 2 with head and neck cancer carcinoma and 1 had renal cell carcinoma. There are 21 males. Twelve patients received pamidronic acid and zoledronic acid sequentially, 11 received zoledronic acid and 3 received pamidronic acid. Fourteen patients had modest increases in serum creatinine concentrations. The mean number of prior chemotherapy / radiation regimens was 3.5. Nine patients received thalidomide and five patients received bortezomib. Primary disease status was as follows: 12 patients were in clinical remission, 5 had stable disease and 10 had progressive disease. Eight patients were on statin therapy ...

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Abstract

Methods of and kits for determining the pharmacogenetic, pharmacokinetic and cellular basis of bisphosphonate-induced osteonecrosis of the jaw (BONJ) involve associating particular proteins and particular single nucleotide polymorphisms with a risk for developing BONJ after receiving bisphosphonate treatment. Methods and kits for identifying the genetic basis for a patient's predisposition to BONJ, and methods of identifying patients who are prone to develop BONJ following bisphosphonate administration provide for the development of a tool for physicians to prescribe treatment protocols for BONJ patients based on the patients' genomes ('personal / tailored medicine'). A haplotype tagging SNP approach was used to analyze candidate genes involved in bone absorption and destruction and to examine the influence of genetic variants on the susceptibility of BONJ. Bone biomarkers of BONJ were examined using molecular cell techniques. The methods described herein can be used to identify differences in how patients are genetically predisposed to BONJ as well as genetic differences amongst patients that account for differences in how these patients clear bisphosphonate s from their systems. Determining such genetic differences provides for improved monitoring of the drugs used to treat BONJ, improved prevention of BONJ, and optimized treatment for patients having BONJ or predisposed to BONJ.

Description

[0001] Cross References to Related Applications [0002] This application claims the benefit of U.S. Provisional Application Serial No. 61 / 292,730, filed January 6, 2010, the entire disclosure of which is hereby incorporated by reference, including all figures, tables, amino acid and nucleic acid sequences; Continuation-in-Part of International Application No. PCT / US2009 / 049767, filed July 7, which claims the benefit of U.S. Provisional Application No. 61 / 078,680, filed July 7, 2008, the disclosures of each of which are hereby incorporated herein by reference , including all figures, tables, amino acid and nucleic acid sequences. field of invention [0003] The present invention relates generally to the fields of molecular biology, genetics and medicine. More particularly, the present invention relates to genetic polymorphisms and protein expression in serum for assessing the risk of osteonecrosis of the jaw in humans receiving or being prescribed bisphosphonates. Backgroun...

Claims

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Application Information

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Patent Type & Authority Applications(China)
IPC IPC(8): C12Q1/68C12N15/12
CPCC12Q2600/156C12Q2600/172C12Q1/6883A61P19/08
Inventor J·凯兹T·Y·兰盖伊
Owner UNIV OF FLORIDA RES FOUNDATION INC
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