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1.
PLoS One ; 15(9): e0238878, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-32915858

RESUMO

Multiple works have studied possible associations between human leukocyte antigen (HLA) alleles and end stage renal disease (ESRD) showing, however, contradictory and inconsistent results. Here, we revisit the association between ESRD and HLA antigens, comparing HLA polymorphism (at HLA-A, -B, -C, -DRB1, -DQB1 and DQA1 loci) in ESRD patients (n = 497) and controls (n = 672). Our data identified several HLA alleles that displayed a significant positive or negative association with ESRD. We also determined whether heterozygosity or homozygosity of the ESRD-associated HLA alleles at different loci could modify the prevalence of the disease. Few HLA allele combinations displayed significant associations with ESRD, among which A*3_26 combination showed the highest strength of association (OR = 4.488, P≤ 0.05) with ESRD. Interestingly, the age of ESRD onset was not affected by HLA allele combinations at different loci. We also performed an extensive literature analysis to determine whether the association of HLA to ESRD can be similar across different ethnic groups. Our analysis showed that at least certain HLA alleles, HLA-A*11, HLA-DRB1*11, and HLA-DRB1*4, display a significant association with ESRD in different ethnic groups. The findings of our study will help in determining possible protective or susceptible roles of various HLA alleles in ESRD.


Assuntos
Haplótipos , Antígenos de Histocompatibilidade Classe I/classificação , Antígenos de Histocompatibilidade Classe I/genética , Falência Renal Crônica/epidemiologia , Falência Renal Crônica/genética , Polimorfismo Genético , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Alelos , Estudos de Casos e Controles , Genótipo , Antígenos HLA-A/genética , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Humanos , Falência Renal Crônica/classificação , Pessoa de Meia-Idade , Paquistão/epidemiologia , Adulto Jovem
2.
Int J Immunogenet ; 47(4): 324-328, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32623831

RESUMO

We analysed data from 80 patients who tested positive for SARS-CoV-2 RNA who had previously been HLA typed to support transplantation. Data were combined from two adjacent centres in Manchester and Leeds to achieve a sufficient number for early analysis. HLA frequencies observed were compared against two control populations: first, against published frequencies in a UK deceased donor population (n = 10,000) representing the target population of the virus, and second, using a cohort of individuals from the combined transplant waiting lists of both centres (n = 308), representing a comparator group of unaffected individuals of the same demographic. We report a significant HLA association with HLA- DQB1*06 (53% vs. 36%; p < .012; OR 1.96; 95% CI 1.94-3.22) and infection. A bias towards an increased representation of HLA-A*26, HLA-DRB1*15, HLA-DRB1*10 and DRB1*11 was also noted but these were either only significant using the UK donor controls, or did not remain significant after correction for multiple tests. Likewise, HLA-A*02, HLA-B*44 and HLA-C*05 may exert a protective effect, but these associations did not remain significant after correction for multiple tests. This is relevant information for the clinical management of patients in the setting of the current SARS-CoV-2 pandemic and potentially in risk-assessing staff interactions with infected patients.


Assuntos
Betacoronavirus/imunologia , Infecções por Coronavirus/imunologia , Predisposição Genética para Doença/genética , Teste de Histocompatibilidade , Pneumonia Viral/imunologia , Alelos , Infecções por Coronavirus/patologia , Frequência do Gene , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Humanos , Transplante de Órgãos , Pandemias , Pneumonia Viral/patologia , Transplantados
3.
Int J Infect Dis ; 97: 47-53, 2020 Aug.
Artigo em Inglês | MEDLINE | ID: mdl-32531432

RESUMO

PURPOSE: To explore the molecular genetic mechanisms underlying different responsiveness to Enterovirus 71 (EV71) vaccine. METHODS: We recruited 10,245 healthy children into a phase 3 clinical trial to evaluate the efficacy of EV71 vaccine in 2012. Fifty subjects from the trial were divided into the potent immune response group (20 subjects) and the ineffective immune response group (30 subjects). Whole-exome sequencing was performed for these 50 samples and we conducted bioinformatics analyses based on online public database. RESULTS: A total of 222,180 germline variants were detected across 50 subjects. Single nucleotide variant (SNV)-based screening of the subjects with potent or ineffective immune response allowed the identification of a potentially detrimental heterozygous missense variant (c.3784C>T) in EEA1. We also retained TRIM59 and ABCA7 genes that contain different loss of function (LoF) variants shared in two cases and involved in the immune response process. Then, we conducted high-resolution typing of 9 classical HLA genes, HLA-DRB1*03:01, HLA-DQA1*05:01 and HLA-DQB1*02:01 alleles were frequently (recurrence ≥5) observed only in ineffective immune responders. CONCLUSIONS: Our study is a meaningful attempt on the comparison of genomic profiles between potent and ineffective immune responders induced by EV71 vaccine, and several candidate potentially detrimental genes were identified.


Assuntos
Enterovirus Humano A/imunologia , Vacinas Virais/imunologia , Transportadores de Cassetes de Ligação de ATP/genética , Alelos , Pré-Escolar , China , Feminino , Variação Genética , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Humanos , Lactente , Peptídeos e Proteínas de Sinalização Intracelular/genética , Masculino , Proteínas com Motivo Tripartido/genética , Sequenciamento Completo do Exoma
4.
J Neuroimmunol ; 344: 577243, 2020 07 15.
Artigo em Inglês | MEDLINE | ID: mdl-32417596

RESUMO

This study was to investigate whether autoimmune encephalitis is associated with the human leukocyte antigen (HLA) genotypes in Chinese Han population. We compared and analyzed the HLA genotypes of 101 patients with autoimmune encephalitis (77 anti-NMDAR, 11 anti-LGI1 and 13 anti-GABABR antibody, respectively) to the 200 healthy control groups. Our results showed that the DRB1*03:01 or DQB1*02:01 allele and the extended DRB1*03:01 ~ DQB1*02:01 haplotype represented the strong susceptibility locus for anti-LGI1 encephalitis (OR = 18.84, 95% CI = 5.01-70.89, Pc = 0.004; OR = 18.84, 95% CI = 5.01-70.89, Pc = 0.004; OR = 18.84, 95% CI = 5.01-70.89, Pc = 0.001). Additionally, the DRB1*08:03 ~ DQB1*06:01 or B*08:01 ~ C*07:02 haplotype was likely to be associated with anti-LGI1 encephalitis (OR = 10.23, 95% CI = 2.87-36.42, Pc = 0.039; OR = 74.62, 95% CI = 6.97-799.06, Pc = 0.043). No statistically significant differences were found for HLA association between patients with anti-NMDAR or anti-GABABR encephalitis and healthy controls. These results indicated that HLA subtypes were only associated with anti-LGI1 encephalitis.


Assuntos
Grupo com Ancestrais do Continente Asiático/genética , Encefalite/diagnóstico , Encefalite/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Doença de Hashimoto/diagnóstico , Doença de Hashimoto/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Adolescente , Adulto , Idoso , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Estudos Prospectivos , Estudos Retrospectivos , Adulto Jovem
5.
Zhonghua Yi Xue Yi Chuan Xue Za Zhi ; 37(6): 681-684, 2020 Jun 10.
Artigo em Chinês | MEDLINE | ID: mdl-32472552

RESUMO

OBJECTIVE: To verify a HLA-DQB1*03:90N allele and method to improve the accuracy of HLA typing. METHODS: A total of 2265 hematopoietic stem cell donors from Shenzhen Branch of China Marrow Donor Program in 2018 were initially detected by a PCR sequence-specific oligonucleotide probe (SSOP) method. Among these, a rare HLA-DQB1 allele was identified by sequence-based tying (SBT) and Ion Torrent S5 next generation sequencing (NGS). RESULTS: The SSOP typing result suggested the HLA-DQB1 to be a rare allele, while an insertion and a deletion was suspected in its exon 2 by SBT, which were confirmed by NGS as DQB1*03:90N and DQB1*06:01, respectively. CONCLUSION: Rare alleles suspected by the SSOP method should be verified by other methods to ensure the accuracy of HLA genotyping. Rare alleles formed by deletions can be detected by NGS with accuracy.


Assuntos
Cadeias beta de HLA-DQ/genética , Alelos , China , Teste de Histocompatibilidade , Humanos
6.
Cancer Res ; 80(12): 2451-2460, 2020 06 15.
Artigo em Inglês | MEDLINE | ID: mdl-32276964

RESUMO

To identify genetic variants for risk of squamous cell carcinoma of the head and neck (SCCHN), we conducted a two-phase genome-wide association study consisting of 7,858,089 SNPs in 2,171 cases and 4,493 controls of non-Hispanic white, of which, 434,839 typed and 7,423,250 imputed SNPs were used as the discovery. SNPs with P < 1 × 10-3 were further validated in the OncoArray study of oral and pharynx cancer (5,205 cases and 3,232 controls of European ancestry) from databases of Genotypes and Phenotypes. Meta-analysis of the discovery and replication studies identified one novel locus 6p22.1 (P = 2.96 × 10-9 for the leading rs259919) and two cancer susceptibility loci 6p21.32 (rs3135001, HLA-DQB1) and 6p21.33 (rs1265081, CCHCR1) associated with SCCHN risk. Further stratification by tumor site revealed four known cancer loci (5p15.33, 6p21.32, 6p21.33, and 2p23.1) associated with oral cavity cancer risk and oropharyngeal cancer risk, respectively. In addition, one novel locus 18q22.2 (P = 2.54 × 10-9 for the leading SNP rs142021700) was identified for hypopharynx and larynx cancer risk. For SNPs in those reported or novel loci, we also performed functional annotations by bioinformatics prediction and expression quantitative trait loci analysis. Collectively, our identification of four reported loci (2p23.1, 5p15.33, 6p21.32, and 6p21.33) and two novel loci (6p22.1 and 18q22.2) for SCCHN risk highlight the importance of human leukocyte antigen loci for oropharyngeal cancer risk, suggesting that immunologic mechanisms are implicated in the etiology of this subset of SCCHN. SIGNIFICANCE: Two novel risk loci for SCCHN in non-Hispanic white individuals highlight the importance of immunologic mechanism in the disease etiology.


Assuntos
Predisposição Genética para Doença , Cadeias beta de HLA-DQ/genética , Peptídeos e Proteínas de Sinalização Intracelular/genética , Neoplasias Laríngeas/genética , Carcinoma de Células Escamosas de Cabeça e Pescoço/genética , Adolescente , Adulto , Idoso , Idoso de 80 Anos ou mais , Biologia Computacional , Feminino , Estudo de Associação Genômica Ampla , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo de Nucleotídeo Único , Locos de Características Quantitativas , Adulto Jovem
7.
Nat Genet ; 52(3): 247-253, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-32066938

RESUMO

Genetic studies have revealed that autoimmune susceptibility variants are over-represented in memory CD4+ T cell regulatory elements1-3. Understanding how genetic variation affects gene expression in different T cell physiological states is essential for deciphering genetic mechanisms of autoimmunity4,5. Here, we characterized the dynamics of genetic regulatory effects at eight time points during memory CD4+ T cell activation with high-depth RNA-seq in healthy individuals. We discovered widespread, dynamic allele-specific expression across the genome, where the balance of alleles changes over time. These genes were enriched fourfold within autoimmune loci. We found pervasive dynamic regulatory effects within six HLA genes. HLA-DQB1 alleles had one of three distinct transcriptional regulatory programs. Using CRISPR-Cas9 genomic editing we demonstrated that a promoter variant is causal for T cell-specific control of HLA-DQB1 expression. Our study shows that genetic variation in cis-regulatory elements affects gene expression in a manner dependent on lymphocyte activation status, contributing to the interindividual complexity of immune responses.


Assuntos
Autoimunidade/genética , Variação Genética , Antígenos HLA/genética , Cadeias beta de HLA-DQ/genética , Ativação Linfocitária/genética , Regiões Promotoras Genéticas/genética , Alelos , Linfócitos T CD4-Positivos , Sistemas CRISPR-Cas , Linhagem Celular , Regulação da Expressão Gênica , Loci Gênicos , Técnicas de Genotipagem , Antígenos HLA/metabolismo , Cadeias beta de HLA-DQ/metabolismo , Humanos , Imunidade Celular , Linfócitos T Reguladores
8.
BMC Med Genet ; 21(1): 40, 2020 02 24.
Artigo em Inglês | MEDLINE | ID: mdl-32093658

RESUMO

BACKGROUND: Sarcopenia is a skeletal muscle disease of clinical importance that occurs commonly in old age and in various disease sub-categories. Widening the scope of knowledge of the genetics of muscle mass and strength is important because it may allow to identify patients with an increased risk to develop a specific musculoskeletal disease or condition such as sarcopenia based on genetic markers. METHODS: We used bioinformatics tools to identify gene loci responsible for regulating muscle strength and lean mass, which can then be a target for downstream lab experimentation validation. Single nuclear polymorphisms (SNPs) associated with various disease traits of muscles and specific genes were chosen according to their muscle phenotype association p-value, as traditionally done in Genome Wide Association Studies, GWAS. We've developed and applied a combination of expression quantitative trait loci (eQTLs) and GWAS summary information, to prioritize causative SNP and point out the unique genes associated in the tissues of interest (muscle). RESULTS: We found NUDT3 and KLF5 for lean mass and HLA-DQB1-AS1 for hand grip strength as candidate genes to target for these phenotypes. The associated regulatory SNPs are rs464553, rs1028883 and rs3129753 respectively. CONCLUSION: Transcriptome Wide Association Studies, TWAS, approaches of combining GWAS and eQTL summary statistics proved helpful in statistically prioritizing genes and their associated SNPs for the disease phenotype of study, in this case, Sarcopenia. Potentially regulatory SNPs associated with these genes, and the genes further prioritized by a scoring system, can be then wet lab verified, depending on the phenotype it is hypothesized to affect.


Assuntos
Hidrolases Anidrido Ácido/genética , Força da Mão , Fatores de Transcrição Kruppel-Like/genética , Polimorfismo de Nucleotídeo Único , RNA Longo não Codificante/genética , Sarcopenia/genética , Magreza/genética , Composição Corporal/genética , Perfilação da Expressão Gênica , Marcadores Genéticos , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla/métodos , Estudo de Associação Genômica Ampla/estatística & dados numéricos , Cadeias beta de HLA-DQ/genética , Humanos , Desequilíbrio de Ligação , Músculo Esquelético/anatomia & histologia , Músculo Esquelético/metabolismo , Tamanho do Órgão/genética , Fenótipo , Locos de Características Quantitativas , Projetos de Pesquisa , Sarcopenia/complicações , Sarcopenia/epidemiologia , Magreza/complicações , Magreza/epidemiologia
10.
PLoS One ; 15(1): e0226546, 2020.
Artigo em Inglês | MEDLINE | ID: mdl-31895924

RESUMO

BACKGROUND: Celiac disease (CD) is a systemic immune-mediated disorder developing in HLA genetically predisposed individuals carrying HLA-DQ2 and/or HLA-DQ8 molecules. Recent evidences supported a predominant importance of HLA-DQB1 locus and, in particular, HLA-DQB1*02 alleles. This diagnosis is poorly considered in Kazakhstan, because of the assumption that CD is not prevalent in this population. OBJECTIVE: To demonstrate that the genetic predisposition to CD in Kazakhstan is not negligible and is actually comparable to Western populations. METHODS: Through the analysis of HLA-DQ genotypes of healthy bone marrow donors from Kazakhstan's national registry, we estimated the HLA-related genetic predisposition to CD in the country. RESULTS: We demonstrated that the frequency of CD-related HLA-DQB1 alleles and, as a consequence, of predisposed individuals to CD in Kazakhstan is significant and comparable to countries with the highest disease prevalence. CONCLUSION: Considering the dietary style in Kazakhstan, including wheat as a staple food, these results provided a preliminary background of knowledge to expect a significant CD prevalence in Kazakhstan and Central Asia by implementing appropriate and cost-effective diagnostic strategies.


Assuntos
Doença Celíaca/epidemiologia , Predisposição Genética para Doença , Cadeias beta de HLA-DQ/genética , Polimorfismo Genético , Padrões de Prática Médica/estatística & dados numéricos , Adolescente , Adulto , Alelos , Estudos de Casos e Controles , Doença Celíaca/genética , Feminino , Genótipo , Humanos , Cazaquistão/epidemiologia , Masculino , Pessoa de Meia-Idade , Prevalência , Adulto Jovem
11.
J Forensic Sci ; 65(1): 166-169, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31408207

RESUMO

Suicide is a worldwide health problem with multiple causes, including genetic factors. The major histocompatibility complex (MHC) is represented by an assembly of gene encoding the human leukocyte antigen (HLA). The purpose of our study was to determine associations between the HLA profiles and predisposition for suicidal behavior. We harvested blood samples from persons with history of suicidal attempts (case group) and persons never exhibiting such behavior (control group). The DNA was extracted and amplified via polymerase chain reaction (PCR) to determine the HLA-DQB1 profiles. Statistical data processing was performed with the Epi Info program. We found that the presence of the HLA-DQB1*02 allele increases the risk of suicidal behavior, while HLA-DQB1*05 alleviates such risk. The genotype that presented the most increased risk for suicidal behavior was found to be HLA-DQB1*02/HLA-DQB1*03. Our study has demonstrated the presence of several associations between HLA profiles and suicidal behavior.


Assuntos
Alelos , Cadeias beta de HLA-DQ/genética , Tentativa de Suicídio , Adulto , Estudos de Casos e Controles , Feminino , Frequência do Gene , Genótipo , Humanos , Masculino , Reação em Cadeia da Polimerase
12.
Nat Rev Cardiol ; 17(3): 145-154, 2020 03.
Artigo em Inglês | MEDLINE | ID: mdl-31519994

RESUMO

Rheumatic heart disease (RHD) is a complication of group A streptococcal infection that results from a complex interaction between the genetic make-up of the host, the infection itself and several other environmental factors, largely reflecting poverty. RHD is estimated to affect 33.4 million people and results in 10.5 million disability-adjusted life-years lost globally. The disease has long been considered heritable but still little is known about the host genetic factors that increase or reduce the risk of developing RHD. In the 1980s and 1990s, several reports linked the disease to the human leukocyte antigen (HLA) locus on chromosome 6, followed in the 2000s by reports implicating additional candidate regions elsewhere in the genome. Subsequently, the search for susceptibility loci has been reinvigorated by the use of genome-wide association studies (GWAS) through which millions of variants can be tested for association in thousands of individuals. Early findings implicate not only HLA, particularly the HLA-DQA1 to HLA-DQB1 region, but also the immunoglobulin heavy chain locus, including the IGHV4-61 gene segment, on chromosome 14. In this Review, we assess the emerging role of GWAS in assessing RHD, outlining both the advantages and disadvantages of this approach. We also highlight the potential use of large-scale, publicly available data and the value of international collaboration to facilitate comprehensive studies that produce findings that have implications for clinical practice.


Assuntos
Loci Gênicos , Febre Reumática/genética , Cardiopatia Reumática/genética , Animais , Genes de Cadeia Pesada de Imunoglobulina , Predisposição Genética para Doença , Estudo de Associação Genômica Ampla , Cadeias alfa de HLA-DQ/genética , Cadeias alfa de HLA-DQ/imunologia , Cadeias beta de HLA-DQ/genética , Cadeias beta de HLA-DQ/imunologia , Humanos , Fenótipo , Febre Reumática/epidemiologia , Febre Reumática/imunologia , Cardiopatia Reumática/epidemiologia , Cardiopatia Reumática/imunologia , Medição de Risco , Fatores de Risco
13.
Hum Immunol ; 81(1): 8-9, 2020 Jan.
Artigo em Inglês | MEDLINE | ID: mdl-31859128

RESUMO

Sixty hundred and forty-one Brazilian individuals from the north and northwestern state of Paraná, southern Brazil, were selected for the study. The HLA-A, -B, -DRB1, -DQA1, and -DQB1 genotyping were performed using rSSO and Micro SSP analysis. These genotype data are available in the Allele Frequencies Net Database under the population name "Brazil Paraná Caucasian" number "AFND3618".


Assuntos
Genótipo , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cadeias alfa de HLA-DQ/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Brasil , Feminino , Técnicas de Genotipagem , Humanos , Masculino
14.
Biomed Res Int ; 2019: 8146937, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31871943

RESUMO

Background and Aims: Traditional Chinese medicine (TCM) has been widely applied in chronic hepatitis B (CHB) supplementary treatment in China. Kidney yang deficiency syndrome (KYDS), one of the most common TCM syndromes of CHB, is more likely to progress to liver cirrhosis or hepatocellular carcinoma than other syndromes. Polymorphisms in the human leucocyte antigen- (HLA-) DQB1 and -DRB1 genes were reported to be associated with hepatitis B virus infection outcomes. Here, we investigated whether HLA-DQB1 and HLA-DRB1 are associated with the classification of CHB TCM syndromes. Methods: We genotyped HLA-DQB1 and HLA-DRB1 alleles in a total of 105 subjects, including 74 CHB patients (28 KYDS and 46 non-KYDS) and 31 healthy individuals from Sichuan Province of Southwest China, by polymerase chain reaction sequence-based typing (PCR-SBT). Moreover, a meta-analysis was carried out for further verification. Results: The proportion of patients with high HBV DNA load (≥2000 IU/ml) in the KYDS group is higher than that in the non-KYDS group (60.70% [17/28] vs. 28.30% [13/46]); P=0.01). The frequencies of HLA-DQB1∗02:01 (P=0.04) and HLA-DRB1∗03:01 (P=0.04) in the KYDS group were significantly increased compared to the non-KYDS group. The gene test and meta-analysis showed that HLA-DRB1∗08:03 confers susceptibility to CHB (odds ratio = 1.57). Conclusion: We found an association between HLA-DRB1/DQB1 polymorphisms and KYDS of CHB. Moreover, KYDS patients of CHB are characteristic with high HBV DNA loads. These findings help to reveal the biological mechanism of KYDS in high risk of CHB progression and suggest a potential prognostic value for disease outcome evaluation.


Assuntos
Alelos , Progressão da Doença , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Hepatite B Crônica/genética , Medicina Tradicional Chinesa , Adulto , China , DNA Viral , Bases de Dados Factuais , Feminino , Predisposição Genética para Doença/genética , Variação Genética , Genótipo , Cadeias HLA-DRB1/sangue , Humanos , Masculino , Pessoa de Meia-Idade , Polimorfismo Genético , Carga Viral
15.
J Assist Reprod Genet ; 36(12): 2515-2523, 2019 Dec.
Artigo em Inglês | MEDLINE | ID: mdl-31758512

RESUMO

PURPOSE: To investigate the validity, accuracy, and clinical outcomes of Karyomapping in preimplantation genetic testing (PGT) for ß-thalassemia combined with human leukocyte antigen (HLA) matching. METHODS: A total of 128 cycles from January 2014 to December 2017 were identified, and 1205 embryos were biopsied. The case group included 88 cycles using Karyomapping for PGT-HLA, compared with 40 cycles using polymerase chain reaction-short tandem repeat (PCR-STR) as the control group. RESULTS: There were significant differences in the HLA matching rate (21.34 vs. 14.37%), the matched transferable embryo rate (9.79 vs. 14.07%), the clinical pregnancy rate (65.08 vs. 41.86%), and the spontaneous miscarriage rate (2.44 vs. 22.22%) between the case and control groups. In the case group, nearly 1/3 (33.37%) of the embryos showed aneuploidy. According to the results of single nucleotide polymorphism (SNP) haplotype analysis, the recombination rates of HBB (hemoglobin subunit beta) and HLA were 11.46% and 5.61% respectively. HLA gene recombination was mostly distributed between HLA-A and HLA-B and the downstream region of HLA-DQB1. In addition, STR analysis could be considered in the case of copy-neutral loss of heterozygosity (LOH) in the region where the HLA gene is located. CONCLUSION: Karyomapping contributes to accurate selection of matched embryos, along with aneuploidy screening. However, STRs assist identification in cases of LOH in the target region.


Assuntos
Antígenos HLA-A/genética , Antígenos HLA-B/genética , Cariotipagem/métodos , Diagnóstico Pré-Implantação , Talassemia beta/diagnóstico , Adulto , Biópsia , Transferência Embrionária , Feminino , Cadeias beta de HLA-DQ/genética , Subunidades de Hemoglobina/genética , Humanos , Perda de Heterozigosidade/genética , Gravidez , Taxa de Gravidez , Talassemia beta/genética , Talassemia beta/patologia
16.
Dis Markers ; 2019: 1409069, 2019.
Artigo em Inglês | MEDLINE | ID: mdl-31781296

RESUMO

Multiple Sclerosis (MS) displays a heterogeneous clinical onset and progression, which are mostly unpredictable, but demyelination of the central nervous system (CNS) leads to substantial deficits of sensory, motor, autonomic, and neurocognitive functions. Considering all genetic studies on MS, including the advanced genome-wide association studies, the risk linked to HLA alleles remains the highest among other susceptibility genetic variants. However, given the genetic variability of HLA alleles in different ethnic groups, we conducted a systematic review of reviews and meta-analyses aiming at summarizing all the results on the association between MS and HLA class II genes. We systematically searched meta-analyses and systematic reviews dealing with MS and HLA in all ethnicities. From 154 records, we included 5 articles collecting HLA data from 15,232 MS patients and 24,194 ethnically matched controls. DRB1∗15 (OR ranging from 1.39 in Chinese Han to 2.59 in Caucasians) and DQB1∗06:02 (OR ranging from 1.91 in Caucasians to 2.49 in Colombian) alleles confer an increased risk for MS transethnically (Caucasians, Chinese, South Americans, Carribeans, Middle Easterners, Japanese, and North Africans). DRB1∗01, DRB1∗09, DRB1∗11, DRB1∗12, and DRB1∗16 alleles were protective, in agreement with the type of amino-acidic (aa) residues (ranging from position 9 to 90) included in pockets 1, 4, 6, 7, and 9, which are most involved in peptide presentation. Changes in aa residues affect the capability of HLA molecules in binding myelin peptides. DQB1∗06:02 risk allele seems to be the most interesting target as humanized mice expressing only DQB1∗06:02 develop MS-like disease mediated by autoimmune reactions against myelin oligodendrocytic basic protein that stabilizes the myelin. Our summary of results from a high number of patients and controls suggests that allelic variants from both DQB1 and DRB1 genes are equally involved in MS susceptibility/protection transethnically.


Assuntos
Predisposição Genética para Doença , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Esclerose Múltipla/patologia , Alelos , Animais , Estudo de Associação Genômica Ampla , Humanos , Esclerose Múltipla/genética , Esclerose Múltipla/imunologia , Fatores de Risco
18.
Genes (Basel) ; 10(9)2019 09 13.
Artigo em Inglês | MEDLINE | ID: mdl-31540313

RESUMO

Latent autoimmune diabetes in adults (LADA) was recently demonstrated to be the most frequent form of adult-onset autoimmune diabetes mellitus. Case-control studies have investigated the relationship between human leukocyte antigen (HLA)-DQB1 and HLA-DRB1 polymorphisms and LADA risk, but their conclusions are inconsistent. This study aimed to more precisely explore the correlation between these HLA gene variants and LADA development. Eight databases, including PubMed, Embase, and Medline, were systematically searched for relevant studies up to September 15, 2018. We performed this retrospective study using meta-analysis and relative predispositional effect (RPE) methods. The meta-analysis results indicated that DQB1*02 (odds ratio (OR) = 1.685, pc < 0.005) and DQB1*06 (OR = 0.604, pc = 0.010) have opposite effects on susceptibility to LADA, while a significant decrease in LADA risk caused by DQB1*05 (OR = 0.764, pc = 0.100) disappeared upon Bonferroni correction. The RPE method confirmed the roles of DQB1*02 (χ² = 46.475, p < 0.001) and DQB1*06 (χ² = 17.883, p < 0.001) and further suggested protective effects of DQB1*05 (χ² = 16.496, p < 0.001). Additionally, the meta-analysis results showed that DRB1*03 (OR = 2.685, pc < 0.013), DRB1*04 (OR = 1.954, pc < 0.013), and DRB1*09 (OR = 1.346, pc < 0.013) are associated with increased LADA risk, while DRB1*12 (OR = 0.600, pc < 0.013) and DRB1*13 (OR = 0.583, pc < 0.013) carriers have a decreased risk of developing LADA. Furthermore, the RPE method revealed that DRB1*03 (χ² = 98.754, p < 0.001), DRB1*04 (χ² = 94.685, p < 0.001), DRB1*09 (χ² = 40.489, p < 0.001), DRB1*01 (χ² = 12.181, p < 0.001), DRB1*07 (χ² = 10.882, p = 0.001), and DRB1*08 (χ² = 5.000, p = 0.025) play protective roles against LADA. LADA showed a close relationship with genetic polymorphisms of HLA-DQB1 and WHLA-DRB1, which could contribute to a better understanding of disease pathogenesis and the identification of predisposing loci in the diagnosis and treatment of LADA.


Assuntos
Diabetes Mellitus Tipo 1/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Polimorfismo de Nucleotídeo Único , Adulto , Humanos
19.
Hum Immunol ; 80(11): 906-907, 2019 Nov.
Artigo em Inglês | MEDLINE | ID: mdl-31558331

RESUMO

A total of 194 Southeast Asia Chinese from Peninsular Malaysia were genotyped for HLA-A, -B, -C -DRB1, and -DQB1 loci using polymerase chain reaction sequence-specific oligonucleotide probe hybridization methods. In this report, the HLA-B, HLA-DRB1 and HLA-DQB1 were in Hardy-Weinberg proportions (HWEP) (p > 0.05). We observed significant deviation from HWEP in HLA-A (p < 0.05) and HLA-C (p < 0.01) loci. This genotype data was available in Allele Frequencies Network Database (AFND) Dos Santos et al. (2016).


Assuntos
Grupo com Ancestrais do Continente Asiático , Genótipo , Antígenos HLA-A/genética , Antígenos HLA-B/genética , Antígenos HLA-C/genética , Cadeias beta de HLA-DQ/genética , Cadeias HLA-DRB1/genética , Alelos , Ásia Sudeste , Frequência do Gene , Genética Populacional , Haplótipos , Teste de Histocompatibilidade , Humanos , Malásia
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