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
