HLA-system in Chinese children with insulin-dependent diabetes mellitus: a strong association with DR3
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Chinese children with insulin-dependent diabetes mellitus (IDDM) show higher frequencies of specific HLA antigens, including AW33, B17, and DR3. These findings may explain the lower incidence of IDDM in this population compared to Westerners.
Area of Science:
- Immunogenetics
- Pediatric Endocrinology
Background:
- Insulin-dependent diabetes mellitus (IDDM) has a variable incidence across different ethnic groups.
- Understanding the genetic predisposition in diverse populations is crucial for IDDM research.
Purpose of the Study:
- To investigate the distribution of Human Leukocyte Antigen (HLA) genotypes in Chinese children with IDDM in Singapore.
- To compare these findings with those in Western populations and explore potential reasons for ethnic differences in IDDM prevalence.
Main Methods:
- Genotyping of HLA-A, B, DR, and MT antigens was performed on 20 Chinese children diagnosed with IDDM.
- Frequencies of specific HLA alleles were compared between IDDM patients and a control group of normal Chinese individuals.
- Statistical analysis included calculating corrected probability values (P) and relative risk (RR) to assess associations.
Main Results:
- Significantly increased frequencies of HLA AW33 (P=0.00094, RR=8.17), B17 (P=0.001, RR=7.55), and DR3 (P=0.0019, RR=6.20) were observed in IDDM children compared to controls.
- HLA AW33, B17, and DR3 were found to be in linkage disequilibrium in the normal Chinese population.
- All DR3-positive IDDM patients (10/10) also carried the B17 antigen. No increased frequency of DR4 or protective antigens was noted.
Conclusions:
- Specific HLA alleles (AW33, B17, DR3) are strongly associated with IDDM in Chinese children.
- The observed genetic associations differ from those typically found in Western populations.
- These genetic variations may contribute to the relatively lower incidence of IDDM among Chinese children.
Abstract:
We studied the distribution of HLA-A, B, and DR and MT1, MT2, MT3 genotypes in all 20 Chinese children with insulin-dependent diabetes mellitus (IDDM) attending the four government pediatric units in Singapore. We found an increase in HLA BW22 but the corrected probability value was not statistically significant. AW33 and B17 were observed in 50% and 55% of IDDM children, respectively, compared with 11% and 13% of normal controls, respectively. The values for AW33 were as follows: corrected P = 0.00094 and relative risk (RR) = 8.17; for B17 they were corrected P = 0.001 and RR = 7.55. In addition, the frequency of DR3 was 50% in IDDM children compared with 14% of normal controls (corrected P = 0.0019, RR = 6.20). AW33, B17, and DR3 are in linkage disequilibrium in our normal Chinese population. All ten patients who were positive for DR3 also had B17. The frequency of DR4 was not increased, and there were no protection IDDM related antigens found. These differences compared with the results in Western populations may contribute to the relative rarity of IDDM among Chinese children.