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Clinical and Vaccine Immunology, August 2009, p. 1146-1150, Vol. 16, No. 8
1071-412X/09/$08.00+0     doi:10.1128/CVI.00105-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.

Autoimmune Type 1 Diabetes Genetic Susceptibility Encoded by Human Leukocyte Antigen DRB1 and DQB1 Genes in Tunisia{triangledown}

Mouna Stayoussef,1 Jihen Benmansour,1 Abdul-Qader Al-Irhayim,2 Hichem B. Said,3 Chiheb B. Rayana,1 Touhami Mahjoub,1 and Wassim Y. Almawi2*

Research Unit of Hematological and Autoimmune Diseases, Faculty of Pharmacy, University of Monastir, Monastir, Tunisia,1 Department of Endocrinology, CHU Farhat Hached, Sousse, Tunisia,3 College of Medicine and Medical Sciences, Arabian Gulf University, Manama, Bahrain2

Received 9 March 2009/ Returned for modification 12 June 2009/ Accepted 15 June 2009

Human leukocyte antigen (HLA) class II genes contribute to the genetic susceptibility to type 1 diabetes (T1D), and susceptible alleles and haplotypes were implicated in the pathogenesis of T1D. This study investigated the heterogeneity in HLA class II haplotype distribution among Tunisian patients with T1D. This was a retrospective case control study done in Monastir in central Tunisia. The subjects comprised 88 T1D patients and 112 healthy controls. HLA-DRB1 and -DQB1 genotyping was done by PCR-sequence-specific priming. Significant DRB1 and DQB1 allelic differences were seen between T1D patients and controls; these differences comprised DRB1*030101 and DQB1*0302, which were higher in T1D patients than in control subjects, and DRB1*070101, DRB1*110101, DQB1*030101, and DQB1*060101, which were lower in T1D patients than in control subjects. In addition, the frequencies of DRB1*030101-DQB1*0201 and DRB1*040101-DQB1*0302 were higher in T1D patients than in control subjects, and the frequencies of DRB1*070101-DQB1*0201 and DRB1*110101-DQB1*030101 haplotypes were lower in T1D patients than in control subjects. Multiple logistic regression analysis revealed the positive association of DRB1*030101-DQB1*0201 and DRB1*040101-DQB1*0302 and the negative association of only DRB1*070101-DQB1*0201 haplotypes with T1D. Furthermore, a significantly increased prevalence of DRB1*030101-DQB1*0201 homozygotes was seen for T1D subjects than for control subjects. Our results confirm the association of specific HLA-DR and -DQ alleles and haplotypes with T1D in Tunisians. The identification of similar and unique haplotypes in Tunisians compared to other Caucasians highlights the need for evaluating the contribution of HLA class II to the genetic susceptibility to T1D with regard to haplotype usage and also to ethnic origin and racial background.

* Corresponding author. Mailing address: Department of Medical Biochemistry, College of Medicine and Medical Sciences, Arabian Gulf University, P.O. Box 22979, Manama, Bahrain. Phone: 973-39717118. Fax: 973-17271090. E-mail: wassim{at}agu.edu.bh

{triangledown} Published ahead of print on 24 June 2009.

Clinical and Vaccine Immunology, August 2009, p. 1146-1150, Vol. 16, No. 8
1071-412X/09/$08.00+0     doi:10.1128/CVI.00105-09
Copyright © 2009, American Society for Microbiology. All Rights Reserved.





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