Class II HLA DNA polymorphisms in type 1 (insulin-dependent) diabetic patients of north Indian origin.
Genetic associations with Type 1 (insulin-dependent) diabetes may be primary or secondary to linkage disequilibrium. Studies of different racial groups should allow these to be distinguished. We have reported that Type 1 diabetes is associated with HLA-DR3 and -DR4 in subjects of North Indian (Punjab) origin and now present the results of a study of HLA class II DNA polymorphisms in this group and in white caucasoid subjects. DR4 in North Indian Type 1 diabetic patients was associated with DQ beta and DX alpha DNA polymorphisms identical to those found in DR4-positive white caucasoid patients. This DQ beta/DX alpha pattern was increased in frequency in North Indian diabetic patients vs control subjects (33.3% vs 8.5%, p less than 0.001, relative risk = 5.12 (95% confidence limits: 1.96-13.4)). A DQ beta polymorphism with very low relative risk for Type 1 diabetes in white caucasoid subjects was also markedly reduced in North Indian diabetic patients vs control subjects (2.3% vs 24.7%, p less than 0.02, relative risk = 0.10 (95% confidence limits: 0.02-0.46)). This pattern was associated with DR2 in white caucasoid subjects, but with DRw6 in North Indians. A DR3-associated DR beta polymorphism was markedly increased in North Indian diabetic patients vs control subjects (90.2% vs 40.7%, p less than 10(-6), relative risk = 12.1 (95% confidence limits: 4.32-33.9)). The DQ subregion may be a primary site of genetic influence on susceptibility to Type 1 diabetes. Further studies in different racial groups will clarify the HLA associations of Type 1 diabetes.
Department of Medicine, University of Birmingham, UK.
J
J
Fletcher
O
O
Odugbesan
C
C
Mijovic
E
E
Mackay
A R
AR
Bradwell
A H
AH
Barnett
D003922:Diabetes Mellitus, Type 1 / Q000235:genetics / Q000276:immunology*; D005006:Ethnicity; D006681:HLA-D Antigens / Q000235:genetics*; D006683:HLA-DQ Antigens / Q000032:analysis / Q000235:genetics*; D006684:HLA-DR Antigens / Q000032:analysis / Q000235:genetics*; D006801:Humans; D007194:India / Q000208:ethnology; D011110:Polymorphism, Genetic; D012016:Reference Values; D006113:United Kingdom; D044465:White People
D006681:HLA-D Antigens; D006683:HLA-DQ Antigens; D006684:HLA-DR Antigens