Polymorphisms of TNF microsatellite marker a and HLA-DR-DQ in diabetes mellitus—a study in 609 Swedish subjects

• Published in: Human Immunology Vol. 67; no. 7; pp. 527 - 534
• Main Authors: Törn, Carina, Hillman, Magnus, Sanjeevi, Carani B., Landin-Olsson, Mona
• Format: Journal Article
• Language: English
• Published: United States Elsevier Inc 01.07.2006
• Subjects: Adolescent; Adult; Aged; Aged, 80 and over; autoimmunity; Basic Medicine; Diabetes Mellitus, Type 1 - genetics; Diabetes Mellitus, Type 2 - genetics; Gene Frequency; Genetic predisposition; Genotype; HLA-DQ Antigens - genetics; HLA-DR3 Antigen - genetics; HLA-DR4 Antigen - genetics; Humans; Immunologi inom det medicinska området; Immunologi inom det medicinska området (Här ingår: Cell- och immunterapi); Immunology in the medical area; Immunology in the Medical Area (including Cell and Immunotherapy); Linkage Disequilibrium; Medical and Health Sciences; Medicin och hälsovetenskap; Medicinska och farmaceutiska grundvetenskaper; Microsatellite Repeats; Middle Aged; Polymorphism, Genetic; risk; Risk Factors; Sweden; Tumor Necrosis Factor-alpha - genetics; Sweden; Genetic predisposition; autoimmunity; risk
• DOI: 10.1016/j.humimm.2006.04.002
• ISSN: 0198-8859; 1879-1166

We explored the importance of the genetic markers microsatellite TNFa, HLA-DR3-DQ2, and DR4-DQ8 in diabetes mellitus. The studied groups comprised autoimmune type 1 ( n=63), nonautoimmune type 1 ( n=35), latent autoimmune diabetes in adults (LADA; n=54), and nonautoimmune type 2 ( n=340) and these patients were compared to 117 healthy controls. HLA genotyping was done with polymerase chain reaction and sequence-specific oligonucleotides. TNFa microsatellites were determined with polymerase chain reaction and fragment size determination. Univariate analysis of these genetic risk factors demonstrated that homozygosity for TNFa2/2 was a significant risk factor for autoimmune type 1 diabetes (odds ratio (OR)=5.82; 95% confidence interval (95%CI) 1.97–17.2), for autoimmune negative type 1 diabetes (OR=4.63; 95%CI 1.32–16.2), and for LADA (OR=3.90; 95%CI 1.21–12.5). Moreover, heterozygosity for HLA-DR3-DQ2/DR4-DQ8 was an important risk factor for autoimmune type 1 diabetes (OR=16.4; 95%CI 3.60–75) as was DR4-DQ8/x (OR=2.52; 95%CI 1.27–4.98). Heterozygosity for HLA-DR3-DQ2/DR4-DQ8 was a risk factor also for LADA (OR=10.0; 95%CI 2.05–48.9). Neither HLA-DR3-DQ2 nor DR4-DQ8 were risk factors for nonautoimmune type 1 or type 2 diabetes. We concluded that heterozygosity for DR3-DQ2/DR4-DQ8 and to some extent homozygosity for TNFa2/2 were risk factors for autoimmune diabetes irrespective of the clinical classification.