University of Khartoum

Predisposing Immunogenetic Factors To Type I Diabetes Mellitus Among Saudis In Riyadh Area, Saudi Arabia

Predisposing Immunogenetic Factors To Type I Diabetes Mellitus Among Saudis In Riyadh Area, Saudi Arabia

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Title: Predisposing Immunogenetic Factors To Type I Diabetes Mellitus Among Saudis In Riyadh Area, Saudi Arabia
Author: Elsheikh, Nezar Abdullah Eltayeb
Abstract: Background: Type 1 diabetes (T1D) is an autoimmune cell-mediated disorder characterized by destruction of insulin-producing beta cells in the pancreas leading to insulin deficiency and serious complications if untreated. Studies implicated a crucial role of genetic factors coupled with environmental triggers in T1D etiopathology. The aim of this study was to investigate the association of HLA class I (HLA-A, HLA-B, and HLA-C), HLA class II (HLA-DRB1, HLA-DQA1, and HLA-DQB1), PTPN-22, CTLA-4, and IL-2RA with T1D in Saudi Children. Materials and Methods: Two hundred and seventy-nine Saudi T1D patients and 424 healthy controls were enrolled in this study. This was a case-control study carried out at King Fahad Medical City, Riyadh, Saudi Arabia between July 2012 and July 2016. Genotyping was performed using reverse sequence-specific oligonucleotide (rSSO) assay using Luminex flow method and TaqMan® assay using real-time polymerase chain reaction (PCR). Allele, haplotype, and genotype frequencies for T1D cases and controls were calculated by direct counting using iterative expectation maximization (EM) algorithm for unknown gametic phase featured by Arlequin software package version 3.5. T1D risk assessment was determined by p-values, Odds ratios (OR) maximum likelihood, and 95% confidence intervals (CI) using SAS software statistical package version 9.3. P-value < 0.05 was set to be significant throughout the study. Results: DR3 and DR4 class II haplotypes were positively associated with T1D (P-values < 0.0001), whereas DR7, DR13, and DR15 haplotypes were negatively associated with T1D (P-values < 0.0001). HLA-A*24-B*08-C*07, HLA-A*68-B*35-C*04, and HLA-A*68-B*08-C*07 class I haplotypes conferred susceptibility to T1D (P-values ≤ 0.002), whereas HLA-A*31-B*51-C*15, and HLA-A*02-B*51-C*16 were protective (P-values ≤ 0.006). HLA-A*24-B*08-C*07-DR3 and HLA-A*68-B*08-C*07-DR3 extended haplotypes have shown positive association with T1D (P-values ≤ 0.0006) in the present study, while HLA-A*02-B*50-C*06-DR7, HLA-A*31-B*51-C*15-DR13, and HLA-A*02-B*07-C*07-DR15 were protective (P-values ≤ 0.01). DR3/DR4, DR3/DR3, and DR4/DR4 genotypes conferred susceptibility to T1D in this study (P-values < 0.0001), whereas DR7/DR13, DR7/15, DR3/DR15, and DR13/DR15 genotypes exerted protection (P-values ≤ 0.032). IL-2RA (rs3118470) C allele was susceptible to T1D in the present study, whereas T allele was protective (P-values < 0.0001). On the other hand, IL-2RA (rs3118470) CC genotype was susceptible to T1D, while TT was protective (P-values ≤ 0.0009). CTLA-4 (rs5742909) TT genotype was positively associated with T1D (P-value = 0.04), whereas CT genotype was protective (P-value = 0.007). IL-2RA (rs706778) CT genotype was susceptible to T1D (P-value = 0.006), but neither alleles nor genotypes of PTPN-22 (rs2476601) were shown any association with T1D in this study. Conclusion: HLA (class I and class II), IL-2RA (rs3118470) and CTLA-4 (rs5742909) polymorphisms were associated with T1D among Saudis. No association between PTPN-22 (rs2476601) and T1D could be shown.
Description: 195 Pages
URI: http://khartoumspace.uofk.edu/123456789/27398
Date: 2018


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