Abstract
BackgroundThe main genomic region controlling the predisposition to type 1 diabetes is the Human Leukocyte Antigens (HLA) class II of the major histocompatibility complex. Association with different HLA types depends also on the studied populations. In our investigation, we tried to measure the phenotypic HLA class II association frequencies of DR3 and/or DR4 antigens, using a serologic method called microlymphocytotoxicity analysis, in diabetic and nondiabetic (ND) subjects originating from the west-Algerian region of Tlemcen. The aim of the present study was to determine which HLA DR antigens represent a high susceptibility to develop the disease in this area. Using a case-control retrospective study design, we randomly recruited ninety-one related subjects, 39 type 1 diabetics and 52 ND as controls, at the Internal Medicine Board of Medical Centre University of Tlemcen.ResultsDR3 antigen frequencies were comparable between the type 1 diabetics and the ND subjects and showed no association with the disease (p = 1.000, OR = 0.95), whereas DR4 and DR3DR4 antigens were associated with susceptibility to develop type 1 diabetes (DR4; OR = 2.10, DR3DR4; OR = 1.30). Also, no incidence for DR3 (p = 0.2646) or DR3DR4 (p = 0.0699) antigen frequencies was related to the sex ratio. However, significant differences in HLA DR4 frequencies between type 1 diabetics and ND were found to be related to sex (p = 0.0085).ConclusionTaken together, our investigation showed that the strongest association with type 1 diabetes was noticed in the presence of HLA DR4 antigens followed by DR3DR4 antigens. This study highlighted a characteristic of Tlemcen population; a history of consanguineous marriages. Association studies between the disease and genetic polymorphisms should be undertaken in a population where consanguinity is more limited to reduce confounding in result interpretations.
Highlights
The main genomic region controlling the predisposition to type 1 diabetes is the Human Leukocyte Antigens (HLA) class II of the major histocompatibility complex
It is currently obvious that the strongest genetic susceptibility of predisposition is allotted to the IDDM1 alleles located in the HLA locus of the chromosome 6p21 [7,8,9], and the nonHLA alleles, the IDDM2 polymorph gene located in the region 5' of the insulin gene (INS) promoter situated on the chromosome 11p15 [10,11]
DR4 and DR3DR4 antigens showed an association with susceptibility to type 1 diabetes (DR4; odds ratios (OR) = 2.10, DR3DR4; OR = 1.30, that is respectively OR confidence interval 1.04–4.24 and 0.60–2.80, 95% CI), in contrast, DR3 antigens showed no association with the disease (OR = 0.95, OR confidence interval 0.48–1.87, 95% CI)
Summary
The main genomic region controlling the predisposition to type 1 diabetes is the Human Leukocyte Antigens (HLA) class II of the major histocompatibility complex. Other regions of the genome were identified as IDDM3, coding for the IGF1 receptor, IDDM4, located near the fibroblast growth factor 3 gene, IDDM5, near the estrogens receptor gene [7] etc. The majority of these regions have no possible statistical criteria allowing them to be clearly linked to the disease [11]. It is mainly HLA alleles that present a high risk of contracting the disease compared to non-HLA alleles [6,12] Due to this, they are qualified as high genetic predictive markers of developing type 1 diabetes in families having a type 1 diabetic member. The disease prediction offered with success the possibility of clinical trials to delay, or even prevent the appearance of type 1 diabetes
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