Kruit Adrian, Grutters Jan C, Gerritsen Wim B M, Kos Snjezana, Wodzig Will K W H, van den Bosch Jules M M, Ruven Henk J T
Heart Lung Centre Utrecht, St. Antonius Hospital, Department of Pulmonology, Koekoekslaan 1, 3435 CM, Nieuwegein, The Netherlands.
Respir Med. 2007 Mar;101(3):510-5. doi: 10.1016/j.rmed.2006.06.025. Epub 2006 Aug 9.
The value of elevated serum angiotensin-converting enzyme (ACE) activity in the diagnosis and follow-up in sarcoidosis is a matter of ongoing debate. This may be at least related to the insertion (I)/deletion (D) polymorphism in the ACE gene (ACE I/D). ACE activity is influenced by the ACE I/D polymorphism. As a consequence, the use of one reference interval instead of three genotype-specific reference intervals for ACE activity may lead to a less precise interpretation of ACE activity.
In order to assess whether determination of ACE activity indeed requires the ACE I/D genotype to be taken into account, we established ACE I/D-corrected reference intervals in healthy, Caucasian volunteers (n=200). In addition, ACE activities in ACE I/D genotyped patients suspected of or having sarcoidosis (n=129) were expressed as the Z-score related to ACE I/D-corrected reference intervals.
Comparison of the Z-score with ACE activity in which ACE I/D is ignored rendered 8.5% misclassification of 'elevated' versus 'normal' ACE or vice versa.
Our data demonstrate a convenient way to circumvent the use of three reference intervals by introducing a Z-score for ACE activity. It also illustrates the need to re-investigating the possible clinical value of serum ACE activity in sarcoidosis by considering ACE I/D.
血清血管紧张素转换酶(ACE)活性升高在结节病诊断和随访中的价值一直存在争议。这可能至少与ACE基因(ACE I/D)中的插入(I)/缺失(D)多态性有关。ACE活性受ACE I/D多态性影响。因此,使用一个参考区间而非三个基因型特异性参考区间来评估ACE活性可能会导致对ACE活性的解读不够准确。
为了评估测定ACE活性时是否确实需要考虑ACE I/D基因型,我们在健康的白种人志愿者(n = 200)中建立了经ACE I/D校正的参考区间。此外,对疑似结节病或患有结节病的ACE I/D基因分型患者(n = 129)的ACE活性以与经ACE I/D校正的参考区间相关的Z评分表示。
将忽略ACE I/D时的Z评分与ACE活性进行比较,发现“升高”与“正常”ACE的误分类率为8.5%,反之亦然。
我们的数据表明,通过引入ACE活性的Z评分,可以方便地避免使用三个参考区间。这也说明有必要通过考虑ACE I/D重新研究血清ACE活性在结节病中的潜在临床价值。