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Allelic expression imbalance of vitamin D receptor 3'- variants in the Hashimoto's thyroiditis


Tokić, Stana; Štefanić, Mario; Mihaljević, Ivan; Glavaš-Obrovac, Ljubica
Allelic expression imbalance of vitamin D receptor 3'- variants in the Hashimoto's thyroiditis // World Journal of Nuclear Medicine, 9 (Suppl 1):S- 107 (2010) / Padhy, AK (ur.).
New Delhi, India: Jagannath Printing Press, 2010. (poster, međunarodna recenzija, sažetak, znanstveni)


Naslov
Allelic expression imbalance of vitamin D receptor 3'- variants in the Hashimoto's thyroiditis

Autori
Tokić, Stana ; Štefanić, Mario ; Mihaljević, Ivan ; Glavaš-Obrovac, Ljubica

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

Izvornik
World Journal of Nuclear Medicine, 9 (Suppl 1):S- 107 (2010) / Padhy, AK - New Delhi, India : Jagannath Printing Press, 2010

Skup
10th Congress of the WFNMB

Mjesto i datum
Cape Town, South Africa, 18-23.2010

Vrsta sudjelovanja
Poster

Vrsta recenzije
Međunarodna recenzija

Ključne riječi
Receptor ; calcitriol ; allelic imbalance ; gene expression ; Hashimoto's thyroiditis ; T-cells

Sažetak
Hashimoto's thyroiditis (HT) is a T-cell mediated organ-specific autoimmune disorder with stronggenetic background. Vitamin D receptor (VDR) induces regulatory and tolerogenic peripheral immunity through functional expression in immune cells. With respect to plausible functional effects of VDR SNPs, we genotyped four 3'-variants (rs1544410, rs7975232, rs731236, and rs9729) to test whether particular SNP-alleles or 3'- restriction haplotypes are associated with VDR mRNA allelic expression imbalance (AEI) or differences in total VDR mRNA expression. HT patients (n=42) and ethnically matched, autoantibody-negative euthyroid controls (n=56) were genotyped using BsmI, ApaI, TaqI, and Hpy188III restriction endonucleases by PCR-RFLP method. Untouched T-lymphocytes were negatively isolated from peripheral blood using magnetic beads procedure Following T-cell isolation, total RNA was extracted and gene expression studied by RT-PCR. ImageQuantTL program was used for relative quantification of RT-PCR bands. An internal control gene was GAPDH. For AEI measurements, normalized heterozygote ratios of genomic RFLP band intensities were used to establish a 95% confidence interval. All cDNA samples showing deviation beyond 95% CI 17.84-42.2 calculated for gDNA, were characterized as having AEI. AEI was measured in Hpy188III heterozygote (Hh) samples and associated rs9729 allelic variants (TG) were used as markers for two extended 3'RFLP haplotypes, “BAtH” and “baTh”. AEI effect on total VDR mRNA levels was analyzed using Spearman-rank correlations. Genotyping data was processed by Kruskall-Wallis test. All genotype sets were in Hardy-Weinberg equilibrium. AEI was detected in 15/50 Hpy188III cDNA samples and all deviated towards the G(h) allele, indicating underexpression of T(H) allele and “BAtH” haplotype in tested population. AEI had no effect on total VDR mRNA levels. Similarly, no haplotype or allele-specific effects on VDR mRNA levels were observed. Furthermore, no association was detected between VDR mRNA levels and casecontrol status. Our results support allele specific VDR mRNA expression in T-lymphocytes, but functional effect of such transcription mechanism remains to be elucidated.

Izvorni jezik
Engleski

Znanstvena područja
Temeljne medicinske znanosti, Kliničke medicinske znanosti



POVEZANOST RADA


Projekt / tema
219-0982914-2176 - Mehanizam bioloških učinaka novih malih molekula na stanice tumora čovjeka (Ljubica Glavaš Obrovac, )
219-2190372-2068 - Polimorfizmi u genu za vitamin D receptor u psorijazi i atopijskom dermatitisu (Mario Štefanić, )

Ustanove
Klinički bolnički centar Osijek,
Akademija medicinskih znanosti,
Medicinski fakultet, Osijek,
Sveučilište J. J. Strossmayera u Osijeku