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- Title
Association Analysis of HLA-B in Type 1 Diabetes in Romanian Families.
- Authors
Guja, Cristian; Guja, Loreta; Ionescu-Tirgoviste, Constantin
- Abstract
Type 1 diabetes (T1DM) is a chronic autoimmune disease determined by multiple genetic and environmental factors. The main diabetes genes reported so far belong to the HLA class II region, HLA-DQB1 and-DRB1 loci. However, multiple reports exist regarding the independent effect of other HLA markers. In order to begin to assess the diabetogenic role of HLA-B alleles for the Romanian population (with one of the lowest reported incidence of T1DM in Europe), we performed high resolution HLA-B typing in 423 nuclear families. The study group comprised 1,515 individuals with 439 T1DM patients (206 male/224 female) and 1,076 unaffected first degree relatives. Genotyping was done by PCR-SSOP. Data were analysed using the Transmission Disequilibrium Test (TDT) and AFBAC (Affected Family-Based Control) using Stata® 8.1 (http://www.stata.com). To establish if the effects of HLA-B alleles are independent, data were analysed by conditional logistic regression using the high resolution HLA-DQB1 and -DRB1 genotypes for the entire study group. We found a significantly increased transmission to diabetic siblings of HLA-B*08 (71.3% transmission, p[sub TDT] = 6.5 x 10[sup -7]), B*15 (69.2% transmission, p[sub TDT] = 0.005), B*41 (74.1% transmission, p[sub TDT] = 0.0002), B*50 (85.7% transmission, p[sub TDT] = 0.00002) and Bw6 alleles (65.7% Wansmission, P[sub TDT] = 2.35 x 10[sup -8]). We also found a significant decreased transmission of HLA B*51 (26.4% transmission, p[sub TDT] = 6.6 x 10[sup -6]) and HLA B*52 (25.8% transmission, P[sub TDT] = 0.007) alleles to diabetics. The transmission of the same alleles to unaffected siblings was not significantly different from 50%. These results were supported by the higher (respectively lower) frequency of these alleles in cases in comparison with pseudocontrols according to the AFBAC analysis (16.6% vs. 7,2% for B*08;6%vs.2.6% for B*15; 6.7% vs. 1.9% for B*41; 4.8% vs. 1.1% for B*50, 69.25% vs. 54.4% for Bw6 and 1.24% vs. 3% for B52). However, when taking into account the DQB1 and DRB1 genotypes, the conditional logistic regression analysis did not support an independent effect of any of the HLA-B alleles. In conclusion, we were unable to demonstrate an independent effect of the HLA-B locus in this sample of Romanian families. However, we cannot rule out the possibility that such effects exist and could be detected using much larger sample sizes.
- Subjects
HLA histocompatibility antigens; GENETICS of diabetes; PEOPLE with diabetes; ROMANIANS; BIOMARKERS
- Publication
Diabetes, 2007, Vol 56, pA289
- ISSN
0012-1797
- Publication type
Article