The Association of Human Leukocyte Antigens Complex with Type 1 Diabetes in the Omani Population

Abstract

Objectives: Identification of the high risk alleles, genotypes and haplotypes of the human leukocyte antigens (HLA) in different populations is beneficial for understanding their roles in type 1 diabetes (T1D) pathogenesis and intervention practices. This study aimed to identify T1D-associated HLA gene alleles in the Omani population. Methods: The present case-control study included 73 diabetic seropositive children (mean age 9.08 ± 3.27 years) attending the paediatric clinic at Sultan Qaboos University Hospital in Muscat, Oman, and 110 healthy controls. HLA–A, -B, -C, -DRB1 and -DQB1 genes were genotyped using a sequence-specific primer polymerase chain reaction (SSP-PCR). Results: Two HLA class I alleles (B*08, B*58) and three class II alleles (DQB1*02, DRB1*03 and DRB1*04) were associated with T1D susceptibility, while one class I (B*51) and three class II (DQB1*05, DQB1*06 and DRB1*16) alleles were associated with T1D protection. HLA-DRB1*03 and DQB1*02 alleles showed the strongest risk association among all alleles. Six DRB1 residues (E9, S11, S13, Y30, V70 and K71) were significantly associated with T1D susceptibility. Heterozygous genotypes, HLA-DRB1*03/*04 and DQB1*02/*03 were significantly associated with T1D susceptibility (P <0.0001, odds ratio [OR] = 63.21 and P = 0.02, OR = 3.63, respectively). Furthermore, a significant combined action of DRB1*03-DQB1*02 haplotype in T1D risk (P = 0.000176, OR = 15) and DRB1*16-DQB1*05 haplotype in protection (P = 0.0312, OR = 0.48) was detected. Conclusion: Known HLA class II gene alleles are associated with T1D in Omani children.

Keywords: Type 1 Diabetes; Human Leukocyte Antigens; Genotype; Alleles; Residues; Haplotypes, Case-Control Study; Oman.