HLA-B*08 Carry a Risk for Type 1 Diabetes among Cow's Milk Exposed Egyptian Infants and Unmarked Linkage Disequilibrium with DR3-DQA1*05-DQB1*02 Haplotype.

ABSTRACT

Type 1 diabetes (T1D) is an autoimmune disease associated with multiple genetics and environmental factors. The aim of the study is to determine the frequency of HLA-B*08 and HLA-B*39 and its linkage disequilibrium with common risk haplotypes DR3-DQA1*05-DQB1*02, and DR4-DQA1-03-DQB1*0302 among T1D Egyptian infants. And assess different environmental factors as early exposure to cow's milk, exclusive breast feeding, mode of delivery and low birth weight. Sixty eight diabetic infants and 120 healthy controls were studied. HLA-DQB1, and DQA1 alleles were identified using homogeneous PCR and oligonucleotide hybridization assays. HLA-B*08 and HLA-B*39 genes were identified using multiplex PCR. The results showed that early exposure to cow's milk before 6 months carry a significant risk for T1D (16% in patients versus 6.6%in control group, P value=0.03). HLA-B*08 frequency was significantly higher among T1D infants than in control group (14.5% in diabetic infants versus 5%in control group, P value=0.024). DR3-DQA1*05-DQB1*02, and DR4-DQA1-03-DQB1*0302 were significantly higher in diabetic infants than controls (P value < 0.001 and 0.004 respectively). HLA-B*08 gene was found in (15.5%) of DR3-DQA1*05-DQB1*02 positive cases while in control group it was found in (13.5%) (P value=0.8). In conclusion, HLA-B*08 gene carry a risk for T1D in Egyptian infants, while DR3-DQA1*05-DQB1*02 haplotype lacks linkage disequilibrium with HLA-B*08 among T1D infants. Further studies are needed to determine which HLA-B gene is strongly linked to DR3-DQA1*05-DQB1*02 haplotype in T1D infants other than HLA-B*08 and HLA-B*18.