The influence of age at onset and gender on the HLA-DQA1, DQB1 association in Chinese children with insulin dependent diabetes mellitus

Abstract

Certain alleles of human leukocyte antigen (HLA)-DR and -DQ genes have been strongly associated with susceptibility and resistance to insulin- dependent diabetes mellitus (IDDM). To further clarify the association of HLA DQ alleles with IDDM and the influence of age at onset and gender on the association with IDDM, we investigated the association of HLA-DQA1, -DQB1 in 54 childhood onset Chinese (21 male) IDDM patients and 65 normal controls by using polymerase chain reaction-sequence specific primer (PCR-SSP). The mean age plus or minus SD at onset of IDDM patients was 8.37 ± 3.54 year old. Our results revealed that the frequencies of DQA1 ∗0301, ∗0302, DQB1 ∗0201, and ∗0302 in IDDM patients were significantly higher than that in the control group ( p < 0.025, < 0.005, < 0.001, and < 0.001, respectively). The frequency of DQA1 ∗0301, ∗0302, DQB1 ∗0201, and ∗0302 were susceptible alleles to IDDM with relative risks of 2.0, 3.5, 5.0 and 4.3, respectively. The protective alleles to IDDM were DQA1 ∗0101, ∗0103, DQB1 ∗0301, ∗0503, and ∗0602. We divided IDDM patients into three groups according to age at onset (1-5, 6-10, and 11-15 years old). The frequency of DQA1 ∗0302 decreased as age increased, and the frequency of DQA1 ∗0501 increased as age increased. Our results also showed that male IDDM patients had higher frequencies of DQA1 ∗0501, DQB1 ∗0201 than female IDDM patients ( p < 0.025 and < 0.025, respectively), while female IDDM patients had higher frequencies of DQB1 ∗0502 than male IDDM patients ( p < 0.05). In our study significant susceptibility haplotypes to IDDM were DQA1 ∗0301-DQB1 ∗0302, DQA1 ∗0501-DQB1 ∗0201, DQA1 ∗0301-DQB1 ∗0201, and DQA1 ∗0302-DQB1 ∗0201.