Polymorphisms of TNF microsatellite marker a and HLA-DR-DQ in diabetes mellitus-a study in 609 Swedish subjects.
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.
Törn
Carina
C
Diabetes Laboratory, Institution of Clinical Sciences, Lund University, Lund, Sweden. Carina.Torn@med.lu.se
Hillman
Magnus
M
Sanjeevi
Carani B
CB
Landin-Olsson
Mona
M
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D003924:Diabetes Mellitus, Type 2 / Q000235:genetics*; D005787:Gene Frequency; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D015803:HLA-DR3 Antigen / Q000235:genetics*; D015804:HLA-DR4 Antigen / Q000235:genetics*; D006801:Humans; D015810:Linkage Disequilibrium; D018895:Microsatellite Repeats; D008875:Middle Aged; D011110:Polymorphism, Genetic; D012307:Risk Factors; D013548:Sweden; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics*
D006683:HLA-DQ Antigens; C053186:HLA-DQ2 antigen; C109756:HLA-DQ8 antigen; D015803:HLA-DR3 Antigen; D015804:HLA-DR4 Antigen; D014409:Tumor Necrosis Factor-alpha