Ethical and Sociocultural Implications of Genetic Testing in Transplantation
Ethical and Sociocultural Implications of Genetic Testing in Transplantation
批准号:
9295961
负责人:
Elisa J Gordon
金额:
$7.83万
依托单位国家:
美国
项目类别:
财政年份:
2016
资助国家:
美国
项目状态:
已结题
起止时间:
2016-06-14 至 2018-05-31
关键词:
AffectAfrican AmericanAllelesAmericanApolipoproteinsAttitudeAwarenessChargeChronic Kidney FailureClinicalCommunitiesCounselingDataDevelopmentDiabetes MellitusDialysis procedureDiseaseDonor personEducationEducational MaterialsEligibility DeterminationEnd stage renal failureEquipoiseEthicsEuropeanEvaluationFocus GroupsFosteringFrequenciesFutureGeneticGenetic CounselingGenetic MaterialsGenetic ResearchGenetic ScreeningGenetic screening methodGenetic studyGenomicsGraft SurvivalGuidelinesHealth Knowledge, Attitudes, PracticeInformed ConsentInterviewKidneyKidney FailureKidney TransplantationLearningLiving DonorsMedicalModelingNational Human Genome Research InstituteNephrologyNonmaleficenceOrganOrgan DonorOutcomePatientsPhysiciansPolycystic Kidney DiseasesPopulationPrecision Medicine InitiativeProviderQualitative MethodsQuality of lifeRelative RisksRenal functionReportingResearchRiskSafetyShapesSiteStructureSurveysTestingTimeTransplantationUnited States National Institutes of HealthVariantbasecase-by-case basisclinical practicedisparity reductionepidemiology studyexpectationgenetic variantimprovedlongitudinal analysispreferenceprematurepreventresearch clinical testingresearch studyscreeningtreatment choiceuptakewillingness
中文摘要
项目概要/摘要
活体供肾移植(LDKT)被推广,以解决肾脏短缺的问题,
移植然而,研究表明,活体供者(LD)患肾衰竭的风险高于
4-6此外,非裔美国人(AA)LD的肾脏损害风险更大,
失败后捐赠比欧洲美国(EA)LD。4,5这些发现产生了提高
移植界对保护LD的安全和改善LD的知情同意的关注。7 -14
遗传学可能有助于解释这种差异。遗传学研究发现,载脂蛋白L1(APOL 1)基因
变异(1-2个等位基因)与主要在AA中的肾衰竭显著相关。15 -19肾
来自携带APOL 1变异体的已故供体的移植物的存活率显著低于来自
20 APOL 1变异体可能解释了为什么AA LD在移植后发生肾衰竭的风险更大。
5,6,20因此,检测AA潜在LD的APOL 1变体可以更好地对它们进行风险分层。
移植界对整合APOL 1基因的态度和做法知之甚少。
纳入AA LD的常规临床评价。没有关于移植中基因检测的指导方针。
虽然支持者认为证据足够有力,足以证明APOL 1测试,但批评者反驳说,
23然而,一些移植中心正在常规使用APOL 1检测,22或根据具体情况进行检测。
基础移植中心的做法在道德上受到指控:(不)使用APOL 1测试可能会伤害AA LD。LDS
在不知情的情况下,变异可能会做出不太明智的决定,并不必要地接受捐赠,
将违反不伤害的伦理原则,因为LD不会从捐赠中获得直接的医疗利益。
相反,通过了解他们有APOL 1变体,LD可能会选择不捐赠以保护自己,
防止接受者获得移植存活率可能较低的肾脏。测试也可能影响AA的
文化身份,这反过来又会影响LD是否愿意使用APOL 1测试。
本研究的目的是评估医生使用的道德和社会文化的影响
对AA LD进行APOL 1检测,并为遗传学制定文化敏感的教育材料,
关于APOL 1检测的问题我们将评估移植界的标准期望,
态度,以及通过全国调查检测AA潜在LD的APOL 1变异的现行做法。
我们也会评估AA LD的信息偏好,态度,并愿意接受APOL测试1
通过半结构化的面试。研究结果将有助于发展对文化敏感的
关于APOL 1检测的遗传咨询教育材料,将由AA焦点小组进行完善
身份证拟议的研究是及时的,因为APOL 1检测可以增加AA潜在LD的安全性,
AA LD结果的差异。这项研究有助于NHGRI的倡议,以更好地了解实施
新兴临床基因组学进入临床实践,32与NIH的精准医学倡议一致。
英文摘要
PROJECT SUMMARY/ABSTRACT
Living donor kidney transplantation (LDKT) is promoted to redress the shortage of kidneys for
transplantation. However, studies show that living donors (LDs) have a greater risk of kidney failure than
healthy non-LDs post-donation.4-6 Moreover, African American (AA) LDs have an even greater risk of kidney
failure post-donation than European American (EA) LDs.4,5 These findings have generated heightened
concerns in the transplant community over protecting LDs' safety and improving LDs' informed consent.7-14
Genetics may help explain this disparity. Genetics research found that Apolipoprotein L1 (APOL1) gene
variants (1-2 alleles) are significantly associated with kidney failure predominantly in AAs.15-19 Kidney
transplants from deceased donors with APOL1 variants had significantly shorter survival than kidneys from
donors without variants.20 APOL1 variants may explain why AA LDs have a greater risk of kidney failure post-
donation than do EA LDs.5,6,20 Thus, testing AA potential LDs for APOL1 variants could better risk stratify them.
Little is known about the transplant community's attitudes about and practices of integrating APOL1 genetic
testing into the routine clinical evaluation of AA LDs. No guidelines exist for genetic testing in transplantation.
While proponents believe that the evidence is strong enough to warrant APOL1 testing,21,22 critics counter that
testing is premature.23 Yet some transplant centers are using APOL1 testing routinely,22 or on a case-by-case
basis. Transplant centers' practices are ethically charged: (not) using APOL1 testing could harm AA LDs. LDs
unknowingly with the variants might make less informed decisions and unnecessarily undergo donation, which
would violate the ethical principle of non-maleficence, as LDs gain no direct medical benefit from donation.25-27
Conversely, by learning they had APOL1 variants, LDs may choose to not donate to protect themselves or
prevent the recipient from getting a kidney with potentially lower graft survival. Testing may also affect AAs'
cultural identity, which in turn could shape attitudes about LDs' willingness to use APOL1 testing.
The objective of this study is to assess the ethical and sociocultural implications of physicians' use
of APOL1 testing for AA LDs, and to develop culturally sensitive educational materials for genetic
counseling about APOL1 testing. We will assess the transplant community's normative expectations,
attitudes, and current practices about testing AA potential LDs for APOL1 variants through a national survey.
We will also assess AA LDs' information preferences, attitudes about, and willingness to be tested for APOL1
variants through semi-structured interviews. The results will inform the development of culturally sensitive
education materials for genetic counseling about APOL1 testing, which will be refined by focus groups with AA
LDs. The proposed study is timely because APOL1 testing could increase AA potential LDs' safety and reduce
disparities in AA LD outcomes. This study facilitates NHGRI's initiative to better understand the implementation
of emerging clinical genomics into clinical practice,32 consistent with the NIH's precision medicine's initiative.33
期刊论文(3)
专著(0)
科研奖励(0)
会议论文
Assessing Multi-level Barriers to Racial Equity in Living Liver Donor Transplantation
-
批准号:10730834
-
项目类别:
-
资助金额:$26.98万
-
财政年份:2023
-
负责人:Elisa J Gordon
-
依托单位:
Informing Ethical Translation of Xenotransplantation Clinical Trials
-
批准号:10279335
-
项目类别:
-
资助金额:$50.08万
-
财政年份:2021
-
负责人:Elisa J Gordon
-
依托单位:
Informing Ethical Translation of Xenotransplantation Clinical Trials
-
批准号:10674525
-
项目类别:
-
资助金额:$46.82万
-
财政年份:2021
-
负责人:Elisa J Gordon
-
依托单位:
Integrating a culturally competent APOL1 genetic testing program into living donor evaluation
-
批准号:10180256
-
项目类别:
-
资助金额:$71.46万
-
财政年份:2021
-
负责人:Elisa J Gordon
-
依托单位:
Optimizing Kidney Transplant Patients' Informed Consent for Increased Risk Donors
-
批准号:8341357
-
项目类别:
-
资助金额:$24.0万
-
财政年份:2012
-
负责人:Elisa J Gordon
-
依托单位:
Optimizing Kidney Transplant Patients' Informed Consent for Increased Risk Donors
-
批准号:8504539
-
项目类别:
-
资助金额:$18.39万
-
财政年份:2012
-
负责人:Elisa J Gordon
-
依托单位:
Quality of Informed Consent for Adult-to-Adult Living Donor Liver Transplantation
-
批准号:8259739
-
项目类别:
-
资助金额:$7.63万
-
财政年份:2011
-
负责人:Elisa J Gordon
-
依托单位:
Quality of Informed Consent for Adult-to-Adult Living Donor Liver Transplantation
-
批准号:8089174
-
项目类别:
-
资助金额:$7.63万
-
财政年份:2011
-
负责人:Elisa J Gordon
-
依托单位:
Self-Care & Outcomes Among Kidney Transplant Recipients
-
批准号:7303293
-
项目类别:
-
资助金额:$12.0万
-
财政年份:2003
-
负责人:Elisa J Gordon
-
依托单位:
Self-Care & Outcomes Among Kidney Transplant Recipients
-
批准号:7278762
-
项目类别:
-
资助金额:$11.65万
-
财政年份:2003
-
负责人:Elisa J Gordon
-
依托单位:
Self-Care & Outcomes Among Kidney Transplant Recipients
-
批准号:6804615
-
项目类别:
-
资助金额:$11.53万
-
财政年份:2003
-
负责人:Elisa J Gordon
-
依托单位:
Self-Care & Outcomes Among Kidney Transplant Recipients
-
批准号:6930988
-
项目类别:
-
资助金额:$11.71万
-
财政年份:2003
-
负责人:Elisa J Gordon
-
依托单位:
Self-Care & Outcomes Among Kidney Transplant Recipients
-
批准号:6596289
-
项目类别:
-
资助金额:$11.26万
-
财政年份:2003
-
负责人:Elisa J Gordon
-
依托单位:
海外基金