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Exp Clin Endocrinol Diabetes 2007; 115(2): 124-129
DOI: 10.1055/s-2007-949589
Article

© J. A. Barth Verlag in Georg Thieme Verlag KG · Stuttgart · New York

HLA, NFKB1 and NFKBIA Gene Polymorphism Profile in Autoimmune Diabetes Mellitus Patients

K. Katarina 1 , P. Daniela 1 , N. Peter 1 , R. Marianna 1 , C. Pavlina 1 , P. Stepanka 2 , L. Jan 2 , T. Ludmila 3 , A. Michal 3 , C. Marie 1
  • 1Department of Molecular and Cell Biology, 3rd Medical Faculty, Charles University, Prague
  • 2Department of Pediatrics, Centrum for Diabetes, metabolism and nutrition research of 3rd Medical Faculty, Charles University, Prague Czech Republic
  • 3Second Internal Clinics, Centrum for Diabetes, metabolism and nutrition research of 3rd Medical Faculty, Charles University, Prague Czech Republic
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Publication History

received 1. 3. 2006 first decision 12. 7. 2006

accepted 26. 7. 2006

Publication Date:
22 February 2007 (online)

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Abstract

Type 1 diabetes mellitus (T1DM) is one of the long-time studied autoimmune disorders. The triggering of the autoimmune process has been ascribed to various genes active in the regulation of the cytokine gene transcription including the Rel/NF-κB gene family. In our study the gene polymorphism of HLA class II, NFKB1 (nuclear factor of kappa light polypeptide gene enhancer in B-cells 1) and NFKBIA (inhibitor of nuclear factor kappa B) was tested. Patients were divided into the subgroups in relation to the disease type: T1DM in children, T1DM in adults, and Latent Autoimmune Diabetes in Adults (LADA). HLA-DRB1*04 and HLA-DQB1*0302 have been detected as risk factors for T1DM in adults and particularly in children (P<0.0001, OR=22.9 and 46.5 respectively). HLA-DRB1*03 has been found as a single risk factor for LADA (P<0.0001, OR=4.9). We detected 15 alleles for the NFKB1 gene polymorphism (CA-repeats) in the Czech population. The alleles were ranging in size from 114-142 bp corresponding to 10-25 CA repeats. Frequency of the A7 allele of NFKB1 gene has been significantly increased in T1DM adults (P<0.01). There was no difference in A and a G allele frequency of NFKBIA gene between the control group and patients, but the association of the AA genotype of NFKBIA gene has been found for LADA (P<0.05). Summarizing our results we concluded that there is a high probability of association of gene polymorphism from Rel/NF-κB family with an autoimmune diabetes course. Due to the results obtained in the epidemiological study we have been looking also for the function significance of the genetic predisposition. No significant changes have been observed by real time PCR testing of HLA-DRB1*04 gene and NFKB1 gene expression between T1DM diabetic group with different HLA, NFKB1, NFKBIA genetic background.

Key words

T1DM - HLA - NFKB1 - NFKBIA - LADA

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1 Funding sources: The project was supported by MSM 0021620814

Correspondence

K. Katarina

Medical Faculty Charles University·Department of Molecular and Cell Biology

Ruská 87

10034 Prague 10

Czech Republic

Phone: +420/26 71 02 66 2

Fax: +420/26 71 02 65 0

Email: katarina.kolostova@post.lf3.cuni.cz

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