Human leukocyte antigen allele linkage disequilibrium and haplotype structure in volunteer bone marrow donors of Paraná State

Abstract Background Bone marrow transplantation has been used in the treatment of various diseases, especially hematologic diseases. The success of this treatment, among other factors, requires human leukocyte antigens (HLA) compatibility between patient and donor. Knowing the human leukocyte antigens allele group and haplotype frequencies as well as the linkage disequilibrium between alleles of different human leukocyte antigens loci can shorten the search time for a compatible bone marrow donor. Objective To assemble and analyze data on human leukocyte antigens frequencies available in the Laboratory of Immunogenetics and Histocompatibility (LIGH) database of the Universidade Federal do Paraná adding an estimation of the Hardy-Weinberg equilibrium and linkage disequilibrium. Methods The sample was composed of seven populations grouped by self-declared ancestry or inferred from the surname as follows: Laboratory of Immunogenetics and Histocompatibility database (all groups), descendants of Italians, Poles, and Asians, Afro-Brazilians, Mulattos (mixed ancestry) and Amerindians. Human leukocyte antigens genotyping was carried out using the polymerase chain reaction-sequence specific primers (PCR-SSP) and -sequence specific oligonucleotide (PCR-SSO) technologies. Results There were high frequencies of the HLA-A*02, HLA-B*35 and HLA-DRB1*13 allelic groups in all groups. The same was observed for the HLA-A*01-B*08-DRB1*03 haplotype except for Asian descendants. It was observed that the human leukocyte antigens Laboratory of Immunogenetics and Histocompatibility database and the Asian group are not in Hardy-Weinberg equilibrium. The Italian, Polish, Asian, Mulatto and Amerindian descendants showed haplotypes in complete linkage disequilibrium. Our results were compared with data on the human leukocyte antigens in the Paraná population available from the Brazilian Voluntary Bone Marrow Donor Registry (REDOME) and data published on the population of Curitiba and the northern region of Paraná. Conclusions Haplotypes frequent in the Asian group were not the most frequently observed in the Laboratory of Immunogenetics and Histocompatibility database and the National Bone Marrow Donor Registry for the state of Paraná. Linkage disequilibrium information may prove useful in the search for bone marrow donors for patients awaiting a suitable donor.

HLA-G e reprodução humana / HLA-G and human reproduction

O gene HLA-G tem sido investigado em várias condições clínicas relacionadas à reprodução. Casais com abortamento espontâneo de repetição, mulheres com pré-eclâmpsia ou que se submetem a tratamentos de reprodução assistida têm participado de estudos caso-controle com o objetivo principal de obter informações que possam esclarecer a participação de HLA-G nessas ocorrências clínicas. Este trabalho traz uma revisão bibliográfica com os estudos principais e mais recentes que descrevem o gene HLA-G e suas isoformas proteicas, bem como a variação genética e polimorfismos que possam influenciar etapas importantes do processo reprodutivo humano. Considerando-se a gestação como uma característica multifatorial, com influência de fatores genéticos e ambientais, não existe um consenso sobre o papel desempenhado pelo gene HLA-G nesse processo. No entanto, variantes alélicas de HLA-G e suas correspondentes isoformas solúveis ou de membrana, têm sido associadas a níveis plasmáticos dos HLA-G e consideradas prognóstico favorável do processo implantacional.

The HLA-G has been investigated in several clinic conditions related to reproduction. Couples with spontaneous recurrent miscarriage, women with preeclampsia or who were submitted assisted reproduction treatments have participated in case-control studies whose main objective was to obtain information that could shed light on the involvement of HLA-G in such clinic conditions. This paper presents a bibliographic revision with the most recent major studies describing HLA-G gene and its protein isoforms, genetic variation and polymorphisms that may influence important stages of the human reproductive process. Considering pregnancy as a multifactorial feature, with the influence of genetic and environmental factors, there is no consensus about the role of HLA-G gene in pregnancy. However, allelic variants of HLA-G and their corresponding soluble or membrane bound isoforms, have been associated with plasma levels sHLA-G and considered a favorable prognosis of the implantation process.

Population analysis of xenobiotic metabolizing genes in South Brazilian Euro and Afro-descendants

Individual variability in xenobiotic metabolism has been associated with susceptibility to developing complex diseases. Genes involved in xenobiotic metabolism have been evaluated in association studies; the difficulty of obtaining accurate gene frequencies in mixed populations makes interpretation of the results difficult. We sought to estimate population parameters for the cytochrome P450 and glutathione S-transferase gene families, thus contributing to studies using these genes as markers. We describe the frequencies of six genes (CYP1A1, CYP2D6, CYP2E1, GSTM1, GSTT1, and GSTP1) and estimate population parameters in 115 Euro-descendants and 196 Afro-descendants from Curitiba, South of Brazil. PCR-based methods were used for genotyping, and statistical analysis were performed by AMOVA with ARLEQUIN software. The mutant allele frequencies in the Afro-descendants and Euro-descendants, respectively, were: CYP1A1*2A = 30.1 percent and 15.2 percent; CYP2D6*4 = 14.5 percent and 21.5 percent; CYP2E1*5B = 7.9 percent and 5 percent; GSTP1*B = 37.8 percent and 28.3 percent. The null genotype frequencies were: GSTM1*0 = 36.8 percent and 46.1 percent; GSTT1*0 = 24.2 percent and 17.4 percent.