Determination of human leukocyte antigen locus polymorphisms in a population of potential stem cell donors in Serbia

Beograd : [Z. P. Andrić]

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Medicina - Transfuziologija / Medicine - Transfusion Medicine

Uvod: Kompleks gena koji kodira sistema humanih leukocitnih antigen (HLA) je najpolimorfniji deo humanog genoma. Složenost polimorfizma HLA je posledica postojanja više genskih lokusa, velikog broja alela za većinu gena i kombinacija produkata ovih alela. Analize polimorfizma HLA i neravnoteže udruživanja alela, kao i razlike učestalosti alela i haplotipova HLA među populacijama, imaju primenu prilikom izbora davaoca za transplantaciju matičnih ćelija hematopoeze i značaj u ispitivanju udruženosti HLA sa etiopatogenezom nekih bolesti. Do sada nije bilo podataka o učestalosti alela i haplotipova alela HLA u populaciji Srbije. Za potrebe transplantacije pacijenata sa ovih prostora, korišćene su dostupne učestalosti alela drugih populacija koje ne moraju nužno da budu identične našoj populaciji. Poznavanje polimorfizma HLA sopstvene populacije bi omogućilo skraćivanje vremena traženja davaoca i pravovremenu transplantaciju MĆH. Takođe, ispitivanje polimorfizma HLA zdrave populacije Srbije je neophodan preduslov da bi se omogućilo dokazivanje relativnog rizika određenih alela HLA kod bolesnika u našoj zemlji. Ciljevi istraživanja: Ciljevi ovog istraživanja su bili da se ustanovi učestalost alela i haplotipova HLA u populaciji Srbije, da se ustanovi stepen genetske sličnosti sa drugim populacijama, kao i da se proceni optimalan broj davalaca u Registru davalaca kostne srži Srbije. Ispitanici i metode: Ispitivanje je rađeno kod zdravih, nesrodnih osoba koje su se prijavile u Registar davalaca kostne srži Srbije. Kod 1992 ispitanika je retrospektivnom analizom određena učestalost alelskih grupa za lokuse HLA-A, HLA-B i HLA-DRB1, kao i učestalost haplotipova HLA-A-B, HLA-A-DRB1, HLA-B-DRB1 i HLA-A-B-DRB1. U podgrupi od 159 slučajno odabranih ispitanika su dodatno određene grupe alela za lokuse HLA-C i HLA-DQ i dobijena je učetsalost gupa alela za ove lokuse, kao i učestalost haplotipova HLA-C-B, HLA-DRB1-DQB1 i HLA-A-B-C-DRB1-DQB1. Dodatno, kod 112 ispitanika kojima su prethodno definisane grupe alela, urađena je tipizacija HLA testovima visoke rezolucije, a potom je određena učestalost alela za svih pet lokusa, kao i učestalost haplotipova dva, tri i pet lokusa...

Introduction: The human leukocyte antigen (HLA) system proteins are products of the most polymorphic genetic system in humans. The complexity of HLA polymorphism is a consequence of multiple gene loci, a large number of alleles for most genes and combinations of these alleles. Analysis of HLA polymorphism and linkeage disequilibrium of alleles, as well as analysis of differences in allele frequency and HLA haplotypes among populations, are applied in the selection of donors for hematopoetic stem cell (HSC) transplantation and have the importance in examining the association of HLA with etiopathogenesis of some diseases. There have been no data on the frequency of alleles and haplotypes of HLA alleles in the population of Serbia. For transplantation of patients from these region were used available allele frequencies of other populations that may not necessarily be identical to our population. Knowledge of HLA polymorphism in own population would allow reducing the search period and timely transplantation of HSCs. Also, knowledge of HLA polymorphism in healthy population of Serbia is a necessary prerequisite to enable the detection of the relative risk of certain HLA alleles for patients in our country. Aims of the investigation: The aims of this study were to determine the frequency of HLA alleles and haplotypes in the population of Serbia, to determine the degree of genetic similarity to other populations, and to estimate the optimal number of donors in the Serbian Bone Marrow Donor Registry. Individuals and methods: The study included healthy, unrelated, randomly selected individuals who were recruited as volunteer donors for Serbian Bone Marrow Donor Registry. Frequency of allelic groups of loci HLA-A, HLA-B and HLA-DRB1, as well as the frequency of HLA-A-B, HLA-A-DRB1, HLA-B-DRB1 and HLA-A-B-DRB1 haplotypes were retrospective analyzed in 1992 individuals. In a subgroup of 159 randomly selected individuals were further defined allele groups for loci HLA-C and HLA-DQ, and estimated the allele group frequencies and the frequency of HLA-C-B, HLA-DRB1-DQB1 and HLA-A-B-C-DRB1-DQB1 haplotypes...

Humani leukocitni antigeni, polimorfizam, populacija Srbije, registar davalaca matičnih ćelija hematopoeze

Human leukocyte antigens, polymorphism, Serbian population, bone marrow donor registry

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