[Association of human leukocyte antigen non-classical genes with type 1 diabetes].
OBJECTIVE
HLA-DMA and DMB are non-classical genes whose product (DM molecules) plays an important role in antigen presentation. Our present study was designed to investigate the relationship between human leukocyte antigen-DMA, -DMB and clinical status heterogeneity of type 1 diabetes.


METHODS
A total of 80 children (male 36, female 44) with type 1 diabetes were selected as research subjects. Diagnosis of type 1 diabetes was made according to WHO criteria. The range of age at onset of type 1 diabetes was 2.5 - 14 years. Ninety-one healthy adult blood donors were selected as normal controls. Polymerase chain reaction and dot blot hybridization techniques were used to classify DMA and DMB alleles. Patients with type 1 diabetes were classified into different groups according to different clinical status, including sex, age of onset, ketosis onset situation on diagnosis, remained function of islet beta cell, etc. Then distribution of DM susceptive alleles and heterodimer in different clinical groups were studied.


RESULTS
The frequencies of DMA * 0103 and DMB * 0103 alleles in patients were significantly increased (50% vs. 8%, 43% vs. 22%, respectively), these two alleles confer susceptibility to type 1 diabetes in Chinese. The frequencies of DMA * 0103/DMB * 0102, DMA * 0103/DMB * 0103 and DMA * 0103/DMB * 0101 heterodimers were also increased in the patients. The above heterodimers confer predisposition to type 1 diabetes. Both DMB * 0103 allele and DM susceptive heterodimers are related to islet beta cell function on diagnosis. The patients with DMB * 0103 allele or DM susceptive heterodimers were significantly increased in the patients with lower C-peptide level on diagnosis (56% vs. 29%; 58% vs. 34% respectively). DM heterodimes were also related to onset age and ketosis-onset-situations of the patients. The patients carrying DM susceptive heterodimers had higher probability to suffer type 1 diabetes before 10 years of age and had the predisposition to ketosis or ketoacidosis on diagnosis.


CONCLUSIONS
HLA- class II non-classical alleles-DMA and DMB may play an important role in pathogenesis of type 1 diabetes, and clinical status heterogeneity of type 1 diabetes may be related to genetic mechanism.
Sang
Yan-mei
YM
Department of Beijing Children's Hospital Affiliated to Capital University of Medical Sciences, Beijng 100045, China.
Yan
Chun
C
Zhu
Cheng
C
Ni
Gui-chen
GC
Hu
Ya-mei
YM
D000293:Adolescent; D000483:Alleles; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics* / Q000473:pathology; D005260:Female; D005787:Gene Frequency; D006681:HLA-D Antigens / Q000235:genetics*; D006801:Humans; D008297:Male; D016133:Polymerase Chain Reaction
D006681:HLA-D Antigens; C084245:HLA-DM antigens