Author/Editor     Maver, A; Medica, I; Salobir, B; Terčelj-Zorman, M; Šabovič, M; Petrovič, D; Peterlin, B
Title     Peroxisome proliferator-activated receptor gamma/PRO12Ala polymorphism and peroxisome proliferator-activated receptor gamma coactivator-1 alpha/gly482Ser polymorphism in patients with sarcoidosis
Type     članek
Source     Sarcoidosis Vasc Diffuse Lung Dis
Vol. and No.     Letnik 25, št. 1
Publication year     2008
Volume     str. 29-35
ISSN     1124-0490
Language     eng
Abstract     Background and aim oft he work:. Reduced expression and activity of the peroxisome proliferator-activated receptor gamma (PPARG) have been measured in cells of bronchoalveolar lavage fluid in sarcoidosis patients. PPARG, together with its transcriptional coactivator peroxisome proliferator-activated receptor gamma coactivator1 alpha (PPARGC1A), has important modulating effects on immune response and apoptosis. In the present study, we investigated whether the polymorphisms Pro12Ala (rs1805192) in the PPARG gene and G1y482Ser (rs8192678) in the PPARGC1A gene, which affect transcriptional activities, are associated with sarcoidosis. Methods: We performed an integrative "omic" approach and identified the PPARG gene as a suitable candidate. Polymerase chain reaction was performed followed by restriction fragment length polymorphism to determine PPARG/Prol2Ala and PPARGC1A/G1y482Ser genotypes of 104 sarcoidosis patients and 112 healthy control subjects. Results: A higher frequency of the Ala allele (p=0.0101, OR=1.84, CI 1.18-2.88), as well as a significantly higher frequency of Pro/Ala heterozygotes and Ala/Ala homozygotes at the Prol2Ala/PPARG polymorphism (p=0.0020, OR=2.45, CI 1.42-4.25) were found in patients with sarcoidosis. In addition, a higher frequency of the Ser allele (p=0.013, OR=1.69, CI 1.13-2.53) and Gly/Ser heterozygotes and Ser/Ser homozygotes (p=0.0470, OR=1.80, CI 1.04-3.10) at the G1y482Ser/PPARGC1A polymorphism were found in patients with sarcoidosis as compared to healthy control subjects. Conclusion: Our results indicate that the presence of the Ala allele at the PPARG/Prol2Ala polymorphism and the Ser allele at the PPARGC1A/G1y482Ser polymorphism may be a predisposing factor for sarcoidosis.
Descriptors     SARCOIDOSIS
BRONCHOALVEOLAR LAVAGE FLUID
GENE EXPRESSION
TRANSCRIPTION FACTORS
POLYMORPHISM, RESTRICTION FRAGMENT LENGTH
POLYMERASE CHAIN REACTION
ALLELES
MICROBODIES
GENOTYPE