High-resolution HLA-A, HLA-B, and HLA-DRB1 haplotype frequencies from the French Bone Marrow Donor Registry

Abstract

Human Leukocyte Antigen G (HLA-G) gene polymorphism and expression rate have recently been suggested to have a potential role in susceptibility to Multiple Sclerosis (MS), a chronic inflammatory demyelinating and neurodegenerative disease of the central nervous system with unknown etiology. The aim of this study was to investigate the association of the frequency of HLA-G gene 14bp insertion/deletion polymorphism and its plasma level to MS susceptibility. In this study, HLA-G gene from 212 patients and 210 healthy individuals was amplified using real time PCR and screened for the 14bp insertion/deletion polymorphism. In addition, HLA-G plasma level of the patients were measured and compared to normal controls by ELISA method. Our results revealed that 14bp insertion in HLA-G could result in lower plasma HLA-G level of the subjects, regardless their health status and vice versa. Additionally, significant correlation of HLA-G genotype and its plasma level to MS susceptibility was observed. In conclusion, not only HLA-G 14bp insertion/deletion polymorphism could be associated to expression rate of the HLA-G gene and its plasma level, but also could be considered as a risk factor for susceptibility to MS in our study population.

Human Leukocyte Antigen-A, B, C, DRB1, and DQB1 Allele and Haplotype Frequencies in a Subset of 237 Donors in the South African Bone Marrow Registry

“…Haplotype frequencies from a specific population may be useful for resolving typing ambiguities using statistical approaches in typing prospective individuals from the same population [ 58 ]. It is important though to note that sample size affects these computations, with a tendency towards haplotype overestimation in small sample-sized studies [ 35 ]. Other confounders include typing ambiguity as previously described [ 59 ].…”

“…These tools use haplotype frequencies to compute the likelihood of a donor-patient match and also anticipate the most likely mismatches. Haplotype frequency may be used to estimate the probability of finding a recipient match or may give an indication of the likelihood of mismatches from initial registry searches [ 35 ]. Additionally, haplotypes are better indicators of HLA match estimation compared to allele frequency alone [ 35 ].…”

“…Frequencies of HLA-A, HLA-B, HLA-C, HLA-DRB1, and HLA-DQB1 alleles and haplotypes were analyzed with the aim of developing a resource for disease association, anthropology, and evolutionary studies. Furthermore, these data will support models for population-specific vaccine development [ 35 ] and will improve donor recruitment strategies in South African populations.…”

Immunogenetics in stem cell donor registry work: The DKMS example (Part 2)

“…HLA-B*58:01 allele frequencies are, for example, 0.81% for German (Schmidt et al, 2009), 0.65% for Polish (Schmidt et al, 2011), 1.02% for French (Gourraud et al, 2015), and-depending on region-between 2.5% and 7.5% for Indian individuals (Maiers et al, 2014 process for this approach. Based on these pilot experiences, the approach may be extended to other DKMS entities and/or other HLAassociated drug reactions.…”

“…For example, carriers of the HLA‐B*58:01 allele have a substantially increased risk for severe cutaneous adverse reactions (SCAR) when exposed to allopurinol, the standard medication against elevated uric acid levels, one of the most often prescribed drugs overall (Aihara, ). HLA‐B*58:01 allele frequencies are, for example, 0.81% for German (Schmidt et al, ), 0.65% for Polish (Schmidt et al, ), 1.02% for French (Gourraud et al, ), and—depending on region—between 2.5% and 7.5% for Indian individuals (Maiers et al, ). If the HLA‐B*58:01 allele carrier status is known, allopurinol should not be prescribed unless no therapeutic alternatives exist.…”