Konda Vani, Huo Dezheng, Hermes Gretchen, Liu Michael, Patel Roshan, Rubin David T
Reva and David Logan Gastrointestinal Clinical Research Center, University of Chicago, Chicago, Illinois 60637, USA.
Inflamm Bowel Dis. 2006 Jun;12(6):497-502. doi: 10.1097/00054725-200606000-00009.
Inflammatory bowel disease (IBD) is a complex genetic disorder characterized by nonmendelian inheritance, incomplete penetrance, and disease susceptibility but not disease certainty. Genotype and phenotype associations are described, but the level of interest of patients with IBD in genetic testing for themselves or at-risk family members remains unknown. Thus, the goal of this study was to assess the interest of patients with IBD in genetic testing and their willingness to accept the uncertainty inherent in complex genetics.
Consecutive outpatients with IBD were recruited to complete a 57-item self-administered survey. The survey included a layperson explanation of the limits of IBD genetics. A 5-point Likert scale was used to determine willingness to undergo genetic testing to determine diagnosis, prognosis, and treatment; to help their family; and to advance medical knowledge. The IBD Questionnaire, a validated measure of the health status attitudes of patients with IBD, was used. To determine limits of patient interest in testing family members, the standard reference gamble paradigm was used. Patients were presented with situations for the genetic test with various levels of certainty in 10% decrements starting with 100%. They indicated the lowest degree of certainty that they would accept to test their family member.
One hundred fourteen patients (mean age 38.4 years; 48.2% women) completed the survey. Of these 114, 71.9% (82) had Crohn's disease. Among the patients who answered questions on self-willingness, 76.8% (86 of 112) would undergo testing for diagnostic confirmation, 81.3% (91 of 112) for prognostic value, 88.4% (99 of 112) for therapeutic decision making, and 85.0% (96 of 113) for advancement of medical knowledge. We found that 28.1% of patients (32 of 114) had a first-degree relative with IBD. Those patients with a first-degree relative with IBD were more willing to undergo genetic testing than those without a first-degree relative with IBD (raw score on self-willingness 4.62 vs 4.36; P=0.026). There was no significant association between patients' health status and their willingness to undergo genetic testing (IBD Questionnaire score and raw score on self-willingness; Spearman's correlation coefficient -0.06; P=0.51). We also found that 88.6% of patients (93 of 105) indicated an interest in testing family members if the test provided absolute certainty of future disease. The average lowest level of certainty these patients were willing to accept was 42.2%.
Despite the complexity of IBD genetics, most patients with IBD are interested in testing and willing to accept a variable degree of uncertainty about the results. An important minority of patients does not wish to be tested. Future work should better identify the reasons for these different attitudes. This information should be factored into plans for widespread clinical testing.
炎症性肠病（IBD）是一种复杂的遗传疾病，其特征为非孟德尔遗传、不完全外显率以及疾病易感性而非疾病确定性。虽然已有基因型与表型关联的描述，但IBD患者对自身或高危家庭成员进行基因检测的关注程度仍不明确。因此，本研究的目的是评估IBD患者对基因检测的兴趣以及他们接受复杂遗传学中固有不确定性的意愿。
连续招募IBD门诊患者完成一份57项的自填式调查问卷。该问卷包括对IBD遗传学局限性的通俗解释。采用5点李克特量表来确定进行基因检测以明确诊断、预后和治疗的意愿；帮助家人的意愿；以及推进医学知识的意愿。使用IBD问卷，这是一种经过验证的衡量IBD患者健康状况态度的工具。为确定患者对检测家庭成员的兴趣限度，采用标准参考赌博范式。向患者呈现基因检测的各种确定性水平的情况，从100%开始以10%的递减幅度。他们指出愿意接受检测其家庭成员的最低确定性程度。
114名患者（平均年龄38.4岁；48.2%为女性）完成了调查。在这114名患者中，71.9%（82名）患有克罗恩病。在回答关于自身意愿问题的患者中，76.8%（112名中的86名）愿意接受检测以确诊，81.3%（112名中的91名）为了预后价值，88.4%（112名中的99名）为了治疗决策，85.0%（113名中的96名）为了推进医学知识。我们发现28.1%的患者（114名中的32名）有IBD的一级亲属。那些有IBD一级亲属的患者比没有IBD一级亲属的患者更愿意接受基因检测（自身意愿原始得分4.62对4.36；P = 0.026）。患者的健康状况与他们接受基因检测的意愿之间没有显著关联（IBD问卷得分与自身意愿原始得分；斯皮尔曼相关系数 -0.06；P = 0.51）。我们还发现，如果检测能提供未来疾病的绝对确定性，88.6%的患者（105名中的93名）表示有兴趣检测家庭成员。这些患者愿意接受的平均最低确定性水平为42.2%。
尽管IBD遗传学复杂，但大多数IBD患者对检测感兴趣并愿意接受结果的不同程度的不确定性。一小部分重要患者不希望接受检测。未来的工作应更好地确定这些不同态度的原因。这些信息应纳入广泛临床检测的计划中。
