Genetic and diabetic auto-antibody markers in Saudi children with type 1 diabetes.
Human leukocyte antigen DRB1 and DQB1 contribute to the genetic susceptibility of type 1 diabetes (T1DM), and they are involved in the induction of the autoimmune destruction of pancreatic beta cells precipitating the disease. The objective of this study was to examine diabetic auto-antibodies (ICA-512, GAD65) and the HLA-DR/DQ genotype among T1DM Saudi children in a cross-sectional study conducted at King Khalid University and National Guard Hospitals, Riyadh. Subjects included in this study were 103 Saudi patients and 180 healthy controls. In all, 41% of patients were positive for ICA512 73.3% positive for GAD65, and 27.3% had both antibodies. The risk alleles were DRB1*0301 (odds ratio [OR] = 11.1); DRB1*0405 (OR = 6.02); DRB1*0401 (OR = 5.8); DQB1*0201 (OR, 17.69) and DQB1*0302 (OR = 3.77). In addition, the DRB1*03/04-DQB1*02/0302 (OR = 123.4) is positively associated with T1DM. However, DRB1*0403 (OR = 0.27), DRB1*1101 (OR = 0.049), DRB1*1307 (OR = 0.28), DRB1*1501 (OR = 0.12), DQB1*0301 (OR = 0.03), DQB1*0401 (OR = 0.04), and DQB1*0602 (OR = 0.16) were protective. Among GAD-positive patients, 81% were DRB1*0301, 68.75% were DQB1*0201, 62.5% were DRB1*0405, 43.75% were DQB1*0302, and 43.7% were DRB1*03/04. Among ICA512-positive patients, all were DRB1*0301, 66.6% were DQB1*0201, 55% were DRB1*0405, 33.3% were DQB1*0302, and 55% were DRB1*03/04. In conclusion, these results show a strong association of HLA-DQB1*0201/0302 and DRB1*03/04 with T1DM. Thus, combining genetic markers with autoantibody is useful in a screening program for early detection of T1DM among Saudi children.
Manan
Hakbany
H
Department of Physiology, College of Medicine and King Khalid University Hospital, King Saud University, Riyadh, Saudi Arabia.
Angham
Al Mutair
AM
Sitelbanat
Awadalla
A
D000293:Adolescent; D017668:Age of Onset; D000483:Alleles; D001323:Autoantibodies / Q000097:blood*; D002648:Child; D002675:Child, Preschool; D003430:Cross-Sectional Studies; D003922:Diabetes Mellitus, Type 1 / Q000175:diagnosis / Q000453:epidemiology / Q000235:genetics* / Q000276:immunology*; D005260:Female; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease; D005968:Glutamate Decarboxylase / Q000276:immunology; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006684:HLA-DR Antigens / Q000235:genetics*; D059811:HLA-DRB1 Chains; D006239:Haplotypes; D006650:Histocompatibility Testing; D006801:Humans; D007223:Infant; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics*; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8 / Q000276:immunology; D012529:Saudi Arabia / Q000453:epidemiology
D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen; D006684:HLA-DR Antigens; D059811:HLA-DRB1 Chains; C553502:HLA-DRB1*03:01 antigen; C553505:HLA-DRB1*04:01 antigen; D008562:Membrane Glycoproteins; C516862:PTPRN protein, human; D054635:Receptor-Like Protein Tyrosine Phosphatases, Class 8; D005968:Glutamate Decarboxylase; C401141:glutamate decarboxylase 2