alexa Association of CTLA-4 Polymorphisms with Type 1 Diabetes in the Egyptian Population
ISSN: 2155-6156

Journal of Diabetes & Metabolism
Open Access

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Research Article

Association of CTLA-4 Polymorphisms with Type 1 Diabetes in the Egyptian Population

Hatem Mohamed Saleh1, Bobby Koeleman2, Gábor Szénási3,4, László Rosivall3,4 and Peter Hamar3,4*

1The Egyptian Organization for Biological Products and Vaccines (EGYVAC-VACSERA), The Egyptian Ministry of Health and Population, Egypt

2Section Research, Department of Medical Genetics, University Medical Center Utrecht, The Netherlands

3Institute of Pathophysiology, Semmelweis University Medical School, Semmelweis University, Hungary

4Hungarian Academy of Sciences, Semmelweis University, Nephrology Research Group, Hungary

*Corresponding Author:
Peter Hamar
Institute of Pathophysiology
Semmelweis University Medical School Budapest
Semmelweis University, 1089, Nagyváradtér 4, Hungary
E-mail: [email protected]

Received date: July 17, 2013; Accepted date: September 16, 2013; Published date: September 20, 2013

Citation: Saleh HM, Koeleman B, Szénási G, Rosivall L, Hamar P (2013) Association of CTLA-4 Polymorphisms with Type 1 Diabetes in the Egyptian Population. J Diabetes Metab 4:291. doi:10.4172/2155-6156.1000291

Copyright: © 2013 Saleh HM, et al. This is an open-access article distributed under the terms of the Creative Commons Attribution License, which permits unrestricted use, distribution, and reproduction in any medium, provided the original author and source are credited.

Abstract

Background: Polymorphisms in the cytotoxic T-lymphocyte antigen 4 (CTLA-4) are associated with the risk of type 1 diabetes (T1D). Here, we investigated the most associated variants CT60 and +49 A/G and five other putative promoter SNPs for their association with T1D in the Egyptian population, a multi-ethnic group. The comparison of disease association between populations can provide further evidence for putative disease variants.

Methods: Association of seven SNPs (-1722,-1661,-651,-319, +49, -819 and +6230G>A) in the CTLA-4 gene with T1D was investigated in 396 patient and 396 control subjects of Egyptian origin. The diagnosis of T1D was made based on ketoacidosis or ketosis with acute onset and severe symptoms of diabetes mellitus at presentation and continuous dependence on insulin. Controls were negative for anti-GAD antibodies and were older than 24 years of age. Genotyping was performed using polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP).

Results: Five of the seven CTLA-4 gene SNPs were associated with T1D with the highest association for +49 A/G in exon 1 (P=0.0002; odds ratio: 1.6, 95% CI 1.3-1.9). Association conditional on SNP +49 A/G was further tested, revealing some independent association for SNPs -1661 and -318. Haplotype analysis of these SNPs demonstrated that no single haplotype was indicative of T1D risk.

Conclusion: The results further support the association of T1D with+49 A/G SNP in the CTLA-4 gene in the Egyptian population. The pattern of association specifically differed from that observed in European and other North African populations, providing further opportunity for fine mapping of genetic disease variants of type-I diabetes.

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