Differential expression of HLA-DQA1 and HLA-DQB1 gene alleles was analysed in three different cell populations isolated from peripheral blood-B lymphocytes, monocytes and whole-blood cells. Interallelic differences in mRNA levels were observed: DQA1*03 alleles were among the most expressed in all cell types, whereas DQA1*05 alleles were least expressed in whole blood and monocytes and among the most expressed in B cells. For DQB1 gene, DQB1*06 group of alleles were the most expressed, and DQB1*02 group the least expressed within all cell populations examined. In comparison with the rest alleles, DQB1*06 and DQB1*05:02 alleles have higher expression in monocytes than in B cells, professional antigen-presenting cells. Cell type-specific regulation of expression was observed as well, with higher and more balanced expression of alleles in B lymphocytes compared to monocytes.
SummaryType 1 diabetes (T1D) belongs among polygenic multifactorial autoimmune diseases. The highest risk is associated with human leucocyte antigen (HLA) class II genes, including HLA-DQA1 gene. Our aim was to investigate DNA methylation of HLA-DQA1 promoter alleles (QAP) and correlate methylation status with individual HLA-DQA1 allele expression of patients with T1D and healthy controls. DNA methylation is one of the epigenetic modifications that regulate gene expression and is known to be shaped by the environment.Sixty one patients with T1D and 39 healthy controls were involved in this study. Isolated DNA was treated with sodium bisulphite and HLA-DQA1 promoter sequence was amplified using nested PCR. After sequencing, DNA methylation of HLA-DQA1 promoter alleles was analysed. Individual mRNA HLA-DQA1 relative allele expression was assessed using two different endogenous controls (PPIA, DRA). We have found statistically significant differences in HLA-DQA1 allele 02:01 expression (PPIA normalization, P corr = 0Á041; DRA normalization, P corr = 0Á052) between healthy controls and patients with T1D. The complete methylation profile of the HLA-DQA1 promoter was gained with the most methylated allele DQA1*02:01 and the least methylated DQA1*05:01 in both studied groups. Methylation profile observed in patients with T1D and healthy controls was similar, and no correlation between HLA-DQA1 allele expression and DNA methylation was found. Although we have not proved significant methylation differences between the two groups, detailed DNA methylation status and its correlation with expression of each HLA-DQA1 allele in patients with T1D have been described for the first time.
Psoriatic arthritis (PsA) affects approximately 30 % of patients suffering from psoriasis vulgaris (PsV), but the risk factors for its development have not been well elucidated yet. The HLA-Cw*06 allele was described as a predisposing factor to PsV. Prolactin is known as an immune response modulator, and its elevated levels present risk for PsV development. It is possible that these factors interact and together emphasize the predisposition to both diseases. We tested on an association of HLA-Cw alleles and functional polymorphism -1149 G/T in PRL gene extrapituitary promoter with PsV and PsA in Czech population. We found a statistically significant association between HLA-Cw*06 allele and PsV (P corrected = 0.0013) that was most prominent in early onset disease subtype (P corrected = 0.0013). The association between HLA-Cw*06 and PsA was low (P corrected = 0.0585) and restricted to PsA patients with early PsV onset (P corrected = 0.0195). We found no association of -1149 G/T PRL gene polymorphism with either PsV or PsA.
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