Naslov
Thyroid Autoantibodies and Vitamin D Receptor Gene 3'-Haplotypes in Graves' Disease and Hashimoto's Thyroiditis

Autori
Štefanić, Mario ; Glavaš-Obrovac, Ljubica ; Tokić, Stana ; Suver, Mirjana ; Karner, Ivan ; Mihaljević, Ivica

Vrsta, podvrsta i kategorija rada
Sažeci sa skupova, sažetak, znanstveni

Izvornik
Eur J Nucl Med Mol Imaging / - , 2009, 473-473

Skup
Annual Congress of the EANM 2009

Mjesto i datum
Barcelona, Španjolska, 10.10.2009. - 14.10.2009

Vrsta sudjelovanja
Poster

Vrsta recenzije
Podatak o recenziji nije dostupan

Ključne riječi
Calcitriol ; Receptor ; Polymorphism ; Restriction Fragment Length ; Graves Disease ; Hashimoto Disease ; Croatia

Sažetak
Abstract: Background: Vitamin D receptor (VDR) signaling exerts potent B, Treg, Th1 and Th17 immunomodulatory activity. Aim: to test whether particular VDR gene 3’ -restriction haplotypes (baT/BAt), previously associated with allelic expression imbalance and differences in total VDR mRNA expression, are implicated in thyroid peroxidase (TPOAb) and thyrotropin receptor antibody (TRAb) production in Graves’ disease (GD) and Hashimoto’ s thyroiditis (HT). Methods: rs1544410 (BsmI), rs7975232 (ApaI) and rs731236 (TaqI) polymorphisms were genotyped by polymerase chain reaction-restriction fragment length polymorphism (RFLP) method in 138 unrelated Caucasian GD individuals (18 male, mean age at diagnosis 41± 11.6 years) and 108 geographically-matched HT cases (8 male, 45± 13.8 years). Two decisions were modeled: the probability to develop antibodies above the threshold level and the level of TAb once they occur. Left-censored, covariate-adjusted Box- Cox Tobit regression that minimizes Pagan-Vella conditional moment test was applied and compared to semiparametric, robust Powell’ s censored least absolute deviation (CLAD) and symmetrically trimmed least squares estimators. Age (GD, HT) and Box-Cox transformed thyrotropin values (HT) were used as covariates ; 104 direct bootstrap replicates were generated to empirically estimate standard errors. The threshold effect and the change effect were derived by McDonald-Moffitt’ s decomposition. Haplotype phases were assigned using Stephens-Donnelly coalescent-based Bayesian method. Pretreatment TPOAb and TRAb- IgG were measured by enzyme-linked immunoassay and radioreceptor assays, respectively, calibrated against WHO and MRC reference standards. Results: In GD group, TPOAb were positive in 75% of cases, with significantly higher median (IQR) levels detected in the HT group [897 (477-2407) vs 246 (47-948) mIU/L, P(exact)=7.8x10-5]. All TPOAb-negative GD cases were TRAb-positive. All genotype frequencies were in Hardy-Weinberg equilibrium. No genotype associations between any of the polymorphisms and TPOAb/TRAb levels were observed in either condition. In contrast, when compared to non- carriers (-/-), BsmI-TaqI Bt and BsmI-ApaI-TaqI BAt haplotype homozygosity, but not heterozygosity, was consistently and positively associated with latent TPOAb variable in GD, but not HT cases [bCLAD=2814± 995, PCLAD=0.0047, bTobit=11.28± 4.1, P=0.006, (Bt/Bt) vs (-/-) ; bCLAD=2826± 986, PCLAD=0.0042, bTobit=11.42± 4.09, P=0.0053, (BAt/BAt) vs (-/-), R2a/CLAD~8.4%, Box-Cox l=0.09, change effect scalar=0.639, threshold effect scalar=0.26]. For TRAb, no effect was observed whatsoever. Conclusion: no consistent evidence for association of two major VDR gene 3’ -haplotypes with TAb status in AITD were obtained. Although background/disease-specific effects may exist, interpretation is complicated by the potential confounding effects of the vitamin D status, tagging properties of the 3’ -RFLPs, imperfect correlation between intrathyroidal synthesis and serum titers of thyroid autoantibodies, data transformations, variable serum clearance rates and sample selection procedures.

Izvorni jezik
Engleski

Znanstvena područja
Kliničke medicinske znanosti

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