The association of Human Leukocyte Antigens Complex with Type 1 Diabetes 7 in Omanis

17 Background: Identifying the human leukocyte antigens (HLA) high risk alleles, genotypes and 18 haplotypes in different populations is beneficial for understanding their roles in type 1 diabetes 19 (T1D) pathogenesis and intervention practices. Objective: The aim of this study was to identify 20 T1D associated HLA gene alleles in the Omani population. Methods: Our case-control study 21 included 73 diabetic seropositive children (mean age 9.08±3.27 years) and 110 healthy controls. 22 HLA–A, -B, -C, -DRB1, and -DQB1 genes were genotyped using sequence specific primer 23 polymerase chain reaction (SSP-PCR). Results: Two HLA class I alleles (B*08, B*58) and three 24 class II alleles (DQB1*02, DRB1*03 and DRB1*04) were associated with T1D susceptibility, 25 while one class I (B*51) and three class II (DQB1*05, DQB1*06, and DRB1*16) alleles were 26 associated with T1D protection. HLADRB1*03 and DQB1*02 alleles showed the strongest risk 27 association among all alleles. Six DRB1 residues (E, S, S, Y, V and K) were significantly 28 associated with T1D susceptibility. Heterozygous genotypes, HLA-DRB1*03/*04 and 29 DQB1*02/*03 were significantly associated with T1D susceptibility (P=4.29E-07, OR=63.2 and 30 P=0.02, OR=3.6, respectively). Furthermore, we detected a significant combined action of 31 DRB1*03-DQB1*02 haplotype in T1D risk (P=1.76E-05, OR=15), and DRB1*16-DQB1*05 32 haplotype in protection (P=3.12E-2, OR=0.48). Conclusion: Known HLA class II gene alleles are 33 associated with T1D in Omani children. 34

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