Next-generation sequencing (NGS) is increasingly used in transplantation settings, but also as a method of choice for in-depth analysis of population-specific HLA genetic architecture and its linkage to various diseases. With respect to complex ethnic admixture characteristic for East Croatian population, we aimed to investigate class-I (HLA-A, -B, -C) and class-II (HLA-DRB1, -DQA1, -DQB1) HLA diversity at the highest, 4-field resolution level in 120 healthy, unrelated, blood donor volunteers. Genomic DNA was extracted and HLA genotypes of class I and DQA1 genes were defined in full-length, -DQB1 from intron 1 to 3' UTR, and -DRB1 from intron 1 to intron 4 (Illumina MiSeq platform, Omixon Twin algorithms, IMGT/HLA release 3.30.0_5). Linkage disequilibrium statistics, Hardy-Weinberg departures, and haplotype frequencies were inferred by exact tests and iterative Expectation-Maximization algorithm using PyPop 0.7.0 and Arlequin v3.5.2.2 software. Our data provide first description of 4-field allele and haplotype frequencies in Croatian population, revealing 192 class-I and class-II alleles and extended haplotypic combinations not apparent from the existing 2-field HLA reports from Croatia. This established reference database complements current knowledge of HLA diversity and should prove useful in future population studies, transplantation settings, and disease-associated HLA screening.

• MeSH
• běloši genetika   MeSH
• dárci krve MeSH
• dospělí MeSH
• frekvence genu MeSH
• haplotypy MeSH
• HLA-A antigeny genetika   MeSH
• HLA-B antigeny genetika   MeSH
• HLA-C antigeny genetika   MeSH
• HLA-DQ alfa řetězec genetika   MeSH
• HLA-DQ beta řetězec genetika   MeSH
• HLA-DRB1 řetězec genetika   MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• sekvenční analýza DNA MeSH
• vazebná nerovnováha MeSH
• vysoce účinné nukleotidové sekvenování MeSH
• zdraví dobrovolníci pro lékařské studie MeSH
• Check Tag
• dospělí MeSH
• lidé středního věku MeSH
• lidé MeSH
• mladý dospělý MeSH
• mužské pohlaví MeSH
• ženské pohlaví MeSH
• Publikační typ
• časopisecké články MeSH
• práce podpořená grantem MeSH
• Geografické názvy
• Chorvatsko MeSH
• Názvy látek
• HLA-A antigeny MeSH
• HLA-B antigeny MeSH
• HLA-C antigeny MeSH
• HLA-DQ alfa řetězec MeSH
• HLA-DQ beta řetězec MeSH
• HLA-DQA1 antigen MeSH Prohlížeč
• HLA-DQB1 antigen MeSH Prohlížeč
• HLA-DRB1 řetězec MeSH

miR-146a has been implicated in the regulation of the immune response as well as in inflammatory process of atherosclerosis. In the present study, we have investigated the expression of miR-146a and its targets, TLR4 a IRAK1, in aortic valve stenosis. A total of 58 patients with aortic stenosis (non- and atherosclerotic; tissue obtained during standard aortic valve replacement) were enrolled. The relative expression of mir-146a was higher in valvular tissue from patients with atherosclerosis compared to those without atherosclerosis (p = 0.01). Number of the IRAK1 and TLR4 transcripts did not differ between the investigated groups. There was a trend toward elevation of miR-146a expression in context of inflammatory infiltrate observed in the valvular tissue from patients with atherosclerosis (p = 0.06). In conclusion, in line with the acknowledged role of miR-146a in atherosclerotic inflammation, our data suggest it may be extended to the specific location of aortic valves in aortic stenosis.

• Klíčová slova
• IRAK1, TLR4, aortic stenosis, epigenetics, microRNA,
• Publikační typ
• časopisecké články MeSH