The Pro12Ala PPARγ gene polymorphism: possible modifier of the activity and severity of thyroid-associated orbitopathy (TAO)
The Pro12Ala PPARγ gene polymorphism: possible modifier of the activity and severity of thyroid-associated orbitopathy (TAO)
复制标题
DOI：
10.1111/j.1365-2265.2008.03343.x
复制
发表时间：
2009-03-01
影响因子：
3.2
通讯作者：
Wiersinga, Wilmar
中科院分区：
文献类型：
--
作者：
Alevizaki, Maria;Mantzou, Emily;Wiersinga, Wilmar
过氧化物酶体增殖物激活受体γ转录因子，参与脂肪形成和炎症，这已经被牵连在甲状腺相关眼眶病（TAO）的发病机制。本研究的目的是探讨与转录活性改变相关的PPAR γ基因Pro（12）Ala多态性可能影响TAO严重程度的可能性。第1组包括172名来自荷兰的TAO患者，他们参加了门诊，阿姆斯特丹学术医学中心内分泌科和轨道中心。第2组包括93例连续的希腊族GD患者，他们没有TAO。在第1组中，记录了眼球突出测量、眼睑水肿、复视（n = 172）和临床活动评分（CAS）（n = 110），始终由同一组的三名研究者进行评估。检测自身抗体水平，等位基因频率为11.5%。GD合并TAO组与GD不合并TAO组的多态性分布无差异。在第1组患者中，Pro（12）Ala携带者的眼球突出显著较低（20.1 +/- 3.3 vs. 22.1 +/- 3.1，P = 0.003，t检验）。PPAR γ多态性携带者的TSH-Rab水平较低（平均等级61.8 vs. 83.2，P = 0.015），CAS较低（110例患者）（平均等级38.9 vs. 55.4，P = 0.022，M-W检验）。随着CAS的增加，多态性频率降低（P = 0.023线性相关）。多因素分析（step）显示，当考虑年龄、吸烟和TSH-Rab水平时，突眼或CAS与PPAR γ基因变异的相关性仍然显著（P < 0.01）。Pro（12）Ala PPAR γ基因多态性在GD伴或不伴TAO患者中的分布相同。在TAO患者中，这种多态性与病情较轻和活动性较低相关。
The PPAR gamma transcription factor, is involved in both adipogenesis and inflammation, which have been implicated in the pathogenesis of thyroid-associated orbitopathy (TAO). The aim of this study was to explore the possibility that the Pro(12)Ala polymorphism of the PPAR gamma gene, associated with a modified transcriptional activity, might be affecting the severity of TAO.We studied two cohorts of patients with Graves' disease (GD): Group 1 comprised 172 patients of Dutch ethnic origin with TAO, who attended the outpatients' clinic, Department of Endocrinology and Orbital Centre of the Academic Medical Centre, Amsterdam. Group 2 comprised 93 consecutive patients with GD of Greek ethnic origin, who did not have TAO. In group 1, exophthalmometry measurements, lid oedema, diplopia (n = 172) and clinical activity score (CAS) (n = 110), always assessed by the same group of three investigators, were recorded. Autoantibody levels were measured.Allele frequency was 11.5%. There was no difference in the distribution of the polymorphism between GD patients with and without TAO. Among group 1 patients proptosis was significantly lower in Pro(12)Ala carriers (20.1 +/- 3.3 vs. 22.1 +/- 3.1, P = 0.003, t-test). PPAR gamma polymorphism carriers had lower TSH-Rab levels (mean rank 61.8 vs. 83.2, P = 0.015) and lower CAS (available in 110 patients) (mean rank 38.9 vs. 55.4, P = 0.022, M-W-test). The frequency of the polymorphism decreased with increasing CAS (P = 0.023 linear by linear association). Multivariate analysis (step) showed that the association of either proptosis or CAS with the PPAR gamma gene variant remained significant when age, smoking and TSH-Rab levels were taken into account (P < 0.01).The distribution of the Pro(12)Ala PPAR gamma gene polymorphism is equally present in patients with GD with or without TAO. Among patients with TAO this polymorphism is associated with less-severe and less-active disease.