Relationship between HLA-DQ and -DR genotypes and clinical characteristics in a French population of Type 1 diabetic patients.
OBJECTIVE
The present study was designed to look for a heterogeneity in the association between Type 1 diabetes mellitus (DM) and class II alleles of major histocompatibility complex (MHC) according to clinical presentation and C-peptide secretion during the first year of the disease, in a population living in south of France.


METHODS
HLA DRB1 and DQB1 genotypes were determined in 129 Caucasoid patients with Type 1 DM and compared to a control group (n = 88). In a subgroup of 46 young adult diabetic patients, basal and postglucagon C-peptide secretion was followed during the first year of the disease (at 0, 1, 3, 6, 9 and 12 months).


RESULTS
The two main haplotypes associated with Type 1 DM were DRB1*04DQB1*0302 and DRB1*03DQB1*02. The genotypes DRB1* 04DQB1 *0302/DRB1*04DQB1*0302 and DRB1 *03DQB1*02/DRB1*04DQB1* 0302 were associated with an early onset of diabetes, while homozygosity for DRB1*03DQB1*02 was characterized by later onset. Levels of residual insulin secretion in patients genotyped DRB1*03DQA1*0501DQB1* 02/DRB1* 04DQA1*0301DQB1*0302 were higher than in patients genotyped DRB1* 3DQA1*0501DQB1*02/DRB1*XDQA1*XDQB1*X or DRB1* XDQA1* XDQB1*X/DRB1*XDQA1*XDQB1*X.


CONCLUSIONS
This study confirms some clinical heterogeneity of Type 1 DM linked to HLA DR and DQ genotypes, and leads to a paradoxical finding: DQB1*02/ DQB1*0302 combination predisposes to an early onset in the whole population but residual secretion of insulin disappears more slowly in a subgroup of young adults with recently diagnosed diabetes. These data suggest that interrelations between MHC genotype and diabetogenic process could be different at various ages of life.
Zevaco-Mattei
C
C
Service de Nutrition, Maladies Métaboliques et Endocrinologie, Hôpital Sainte-Marguerite, Marseille, France. bvialett@mail.ap.hm.fr
Reviron
D
D
Atlan-Gepner
C
C
Botti
G
G
Simonin
G
G
Lassmann-Vague
V
V
Vague
P
P
Mercier
P
P
Vialettes
B
B
D000293:Adolescent; D000328:Adult; D000483:Alleles; D000704:Analysis of Variance; D002648:Child; D002675:Child, Preschool; D003922:Diabetes Mellitus, Type 1 / Q000188:drug therapy / Q000276:immunology*; D005260:Female; D005602:France; D005802:Genes, MHC Class II; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D006684:HLA-DR Antigens / Q000235:genetics*; D006239:Haplotypes; D006801:Humans; D007004:Hypoglycemic Agents / Q000627:therapeutic use*; D007328:Insulin / Q000378:metabolism / Q000627:therapeutic use*; D000078790:Insulin Secretion; D008297:Male; D010641:Phenotype; D011110:Polymorphism, Genetic
D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens; D007004:Hypoglycemic Agents; D007328:Insulin