RESUMO
The B*14:41N allele was identified in a The National Marrow Donor Program (NMDP) Hispanic donor typed by our Mexican Registry-DONORMO.
Assuntos
Antígeno HLA-B14/genética , Hispânico ou Latino/genética , Sistema de Registros , Doadores não Relacionados , Sequência de Bases , Medula Óssea , Éxons/genética , Humanos , México , Dados de Sequência Molecular , Alinhamento de SequênciaRESUMO
The A*29:47 allele was identified in a Mexican Mestizo unrelated bone marrow donor from the state of Hidalgo.
Assuntos
Transplante de Medula Óssea , Antígenos HLA-A/genética , Sequência de Bases , Éxons/genética , Frequência do Gene , Teste de Histocompatibilidade , Humanos , Masculino , México , Pessoa de Meia-Idade , Dados de Sequência Molecular , Mutação/genética , Filogenia , Estabilidade Proteica , Doadores de TecidosRESUMO
Studies of the effect of minor H antigen mismatching on the outcome of renal transplantation are scarce and concern mainly single center studies. The International Histocompatibility and Immunogenetics Workshops (IHIW) provide a collaborative platform to execute crucial large studies. In collaboration with 16 laboratories of the IHIW, the role of 15 autosomal, 10 Y-chromosome encoded minor H antigens and 3 CD31 polymorphisms, was investigated in relation to the incidence of renal graft rejection and graft loss in 444 human leukocyte antigens (HLA)-identical sibling renal transplantations. Recipient and donor DNA samples were genotyped for the minor H antigens HA-1, HA-2, HA-3, HA-8, HB-1, ACC-1, ACC-2, SP110, PANE1, UGT2B17, C19Orf48, LB-ECGF-1, CTSH, LRH-1, LB-ADIR and HY. The correlation between minor H antigen mismatch and the primary outcome graft rejection or graft loss was statistically analyzed. The incidence of rejection was very low and no correlation was observed between one or more minor H antigen mismatch(es) and a rejection episode (n = 36), of which only eight resulted in graft loss. In summary, in our study cohort of 444 renal transplants, mismatching for neither autosomal nor HY minor H antigens correlate with rejection episodes or with graft loss.
Assuntos
Antígenos HLA/imunologia , Teste de Histocompatibilidade , Transplante de Rim/efeitos adversos , Antígenos de Histocompatibilidade Menor/imunologia , Irmãos , Estudos de Coortes , Rejeição de Enxerto/imunologia , HumanosRESUMO
In the last fifteen years, published reports have described KIR gene-content frequency distributions in more than 120 populations worldwide. However, there have been limited studies examining these data in aggregate to detect overall patterns of variation at regional and global levels. Here, we present a summary of the collection of KIR gene-content data for 105 worldwide populations collected as part of the 15th and 16th International Histocompatibility and Immunogenetics Workshops, and preliminary results for data analysis.
Assuntos
Variação Genética , Histocompatibilidade/genética , Receptores KIR/genética , Etnicidade/genética , Frequência do Gene , Genética Populacional , Haplótipos , Humanos , Imunoglobulinas/genética , LigantesRESUMO
A*02:336 was identified in a Mexican Mestizo ALL patient, born in the State of Veracruz.
Assuntos
Alelos , Etnicidade/genética , Antígeno HLA-A2/genética , Leucemia-Linfoma Linfoblástico de Células Precursoras , Sequência de Bases , Pré-Escolar , Éxons/genética , Humanos , Masculino , México/etnologia , Dados de Sequência Molecular , Leucemia-Linfoma Linfoblástico de Células Precursoras/genéticaRESUMO
The killer immunoglobulin-like receptor (KIR) anthropology component of the 15th International Histocompatibility Workshop (IHIWS) sought to explore worldwide population variation in the KIR loci, and to examine the relationship between KIR genes and their human leukocyte antigen (HLA) ligands. Fifteen laboratories submitted KIR genotype and HLA ligand data in 27 populations from six broad ethnic groups. Data were analyzed for correlations between the frequencies of KIR and their known HLA ligands. In addition, allelic typing was performed for KIR2DL2 and 3DL1 in a subset of populations. Strong and significant correlations were observed between KIR2DL2, 2DL3 genotype frequencies and the frequency of their ligand, HLA-C1. In contrast, only weak associations were seen for 3DL1, 3DS1 and the HLA-Bw4 ligand. Although some aspects of the correlations observed here differ from those reported in other populations, these data provide additional evidence of linked evolutionary histories for some KIR and HLA loci. Investigation of allele-level variation for the B haplotype locus KIR 2DL2 showed that two alleles, *001 and *003, predominate in all populations in this study. Much more allelic variation was observed for the A haplotype locus 3DL1, with several alleles observed at moderate frequencies and extensive variation observed between populations.
Assuntos
Evolução Molecular , Variação Genética , Antígenos HLA/genética , Receptores KIR/genética , Loci Gênicos , Genótipo , Antígenos HLA/imunologia , Humanos , Polimorfismo Genético , Receptores KIR/imunologiaRESUMO
DRB1*1532 allele was identified in a Mexican unrelated marrow donor from the Gulf of Mexico.
Assuntos
Alelos , Cidades , Antígenos HLA-DR/genética , Indígenas Norte-Americanos/genética , Doadores de Tecidos , Pareamento Incorreto de Bases , Sequência de Bases , Células da Medula Óssea/citologia , Códon , DNA/genética , DNA/isolamento & purificação , Éxons , Feminino , Variação Genética , Genótipo , Cadeias HLA-DRB1 , Haplótipos , Teste de Histocompatibilidade/métodos , Humanos , Leucócitos/química , México , Dados de Sequência Molecular , Mutação Puntual , Reação em Cadeia da Polimerase , Padrões de Referência , Análise de Sequência de DNA/métodos , Terminologia como Assunto , Adulto JovemRESUMO
Human leukocyte antigen-B*9550 is a novel allele identified in a Mexican Mestizo bone marrow donor from Veracruz.
Assuntos
Substituição de Aminoácidos/genética , Medula Óssea/imunologia , Antígenos HLA-B/genética , Alelos , Sequência de Bases , Éxons/genética , Humanos , Doadores Vivos , México , Dados de Sequência Molecular , Alinhamento de SequênciaAssuntos
Transplante de Medula Óssea , Antígeno HLA-B35/genética , Adulto , Sequência de Bases , Teste de Histocompatibilidade , Humanos , Masculino , México , Dados de Sequência Molecular , Polimorfismo de Nucleotídeo Único , Sistema de Registros , Alinhamento de Sequência , Doadores de Tecidos , Voluntários , Adulto JovemRESUMO
Neurocysticercosis (NC) is caused by the establishment of the metacestode stage of Taenia solium in the human central nervous system. A great heterogeneity in the susceptibility to the infection and to the disease has been reported. While the factors involved in this heterogeneity are not completely understood, clearly different immune-inflammatory profiles have been associated to each condition. This study evaluated the association of cytokine single nucleotide polymorphisms (SNPs) with susceptibility to infection and disease severity in NC patients. Blood samples from 92 NC cases and their parents (trios) were genotyped for SNPs in five cytokines relevant for the immune response: IL4 (-589C/T), IL6 (-174C/G), IFNG (+874T/A), TNF (-238G/A), and IL2 (-330G/T). Specific DNA fragments were amplified by the polymerase chain reaction, using the 5'-nuclease Taqman assay on a 7500 platform, allowing the detection of the polymorphism genotypes. No association between the polymorphisms evaluated neither with susceptibility to infection nor with disease severity was found, although previous studies reported variations in the levels of these cytokines among different NC clinical pictures. These results, nevertheless, add new elements to our understanding of the complex pathogenic mechanisms involved in susceptibility to infection by T. solium cysticerci and the severity of the ensuing disease.
Assuntos
Sistema Nervoso Central/parasitologia , Interferon gama/genética , Interleucina-2/genética , Interleucina-4/genética , Interleucina-6/genética , Neurocisticercose/genética , Taenia solium/fisiologia , Teníase/genética , Fator de Necrose Tumoral alfa/genética , Animais , Progressão da Doença , Frequência do Gene , Estudos de Associação Genética , Predisposição Genética para Doença , Genótipo , Humanos , Linhagem , Polimorfismo de Nucleotídeo ÚnicoRESUMO
There is an emerging use of flow cytometry to evaluate patients with myelodysplastic syndrome (MDS). We have studied CD7 and TdT expression in the CD34+ myeloid blast cell population in 55 bone marrow samples of patients with MDS. CD7 and/or TdT were detected in 38 out of 55 patients (69%). CD7 expression was not related to other bad prognosis data but conversely, we found an association between TdT+ CD34 myeloblasts and high-risk MDS patients according to the International Prognostic Scoring System. Therefore, CD7 and TdT may help to establish the diagnosis of MDS and, TdT expression also seems to be a useful marker in distinguishing risk groups.
Assuntos
Antígenos CD34/biossíntese , Antígenos CD7/biossíntese , DNA Nucleotidilexotransferase/biossíntese , Células Precursoras de Granulócitos/imunologia , Síndromes Mielodisplásicas/imunologia , Adulto , Idoso , Idoso de 80 Anos ou mais , Antígenos CD7/análise , Análise Citogenética , DNA Nucleotidilexotransferase/análise , Feminino , Citometria de Fluxo , Seguimentos , Humanos , Imunofenotipagem , Masculino , Pessoa de Meia-Idade , Síndromes Mielodisplásicas/diagnóstico , Fatores de Risco , Taxa de SobrevidaRESUMO
Undernutrition was induced in rats submitted to food restriction from the fetal stage, and malnutrition was continued after birth until 70 days of life. Body weight was decreased to less than 50%. Plasma T4 and T3 and pituitary TSH content were determined between 8-70 days of life. In control rats, plasma T4 and T3 reached a maximum at 14 and 35 days of life, respectively, and TSH pituitary content at 45 days of life. In undernourished rats, after 8 days of life, plasma T4 and T3 and pituitary TSH content were decreased to about 50% or less, and the pattern of sequential changes observed in control rats was absent or modified. T4 and T3 concentrations were measured in heart, liver, and brain in the fetus (22 days old) and 8, 14, and 23 days after birth, as well as liver and brain 5'-deiodinases (5'D). Hepatic 5'D type I was always decreased in undernourished rats from 8-70 days after birth. Liver and heart T4 and T3 concentrations were decreased in 14-day-old undernourished rats as well as brain T3. Brain 5'D type II was decreased at 8 and 14 days, and total brain 5'D activities at 8 days. These changes occurred during the critical period for brain development (7th to 20th day) during which most processes of myelination take place and T3 brain normal levels are required.
Assuntos
Encéfalo/metabolismo , Iodeto Peroxidase/metabolismo , Fígado/metabolismo , Distúrbios Nutricionais/fisiopatologia , Hipófise/metabolismo , Tireotropina/metabolismo , Tiroxina/metabolismo , Tri-Iodotironina/metabolismo , Envelhecimento , Animais , Peso Corporal , Encéfalo/crescimento & desenvolvimento , Desenvolvimento Embrionário e Fetal , Feminino , Coração/crescimento & desenvolvimento , Fígado/crescimento & desenvolvimento , Miocárdio/metabolismo , Tamanho do Órgão , Especificidade de Órgãos , Hipófise/crescimento & desenvolvimento , Gravidez , Propiltiouracila/farmacologia , Ratos , Ratos Endogâmicos , Valores de Referência , Tri-Iodotironina Reversa/metabolismoRESUMO
Mexican Mestizos, who are the result of the admixture of Spanish, Indian, and Black genes, were analyzed for different systems. Three populations from geographical distinct areas were studied: the north (State of Nuevo Leon ), the center (State of Guanajuato), and the highlands (mainly Mexico City). Ten blood group systems (N = 229), STRs (N = 107), HLA-A*, B*, C* (N = 116-167), and DRB1, DQA1, and DQB1 (N = 40, 101, 160, respectively) were analyzed in the samples of the highlands. The three groups cluster together in the same branch: Mestizos from Venezuela, Mediterranean and Jews close to the cluster of Orientals, followed by Amerindians. All markers demonstrate that Indian genes are strongly represented in the highlands: Di(a), O, D(-)(+), s, A*0201, *0206, B*1539 (*1541), *3902, *3905, *3512, *3517, *4002, *4005, Cw*0801, *0304, *0401 among others. Cw*0501, *1203, *1204, and *1601 are of White ancestry. The most frequent haplotypes *0407-*03011-*0302 and *0802-*0401-*0402 are of Indian descent as well. The center and mainly the north show a more Caucasian and Semitic profile. The results demonstrate the high variability resulting from interethnic admixture, suggesting that this mechanism is the main factor responsible for the large diversity found in urban populations.
Assuntos
Antígenos de Grupos Sanguíneos/genética , Genes MHC da Classe II/genética , Genes MHC Classe I/genética , Indígenas Norte-Americanos/genética , Repetições de Microssatélites/genética , Adulto , Feminino , Antígenos HLA/genética , Haplótipos/genética , Humanos , Masculino , México , Hibridização de Ácido Nucleico , Sondas de Oligonucleotídeos , Reação em Cadeia da Polimerase , Sequências de Repetição em Tandem/genética , Tirosina 3-Mono-Oxigenase/genéticaRESUMO
To analyze the contribution of MHC class II genes in type 2 diabetes mellitus (DM) with end stage renal disease (ESRD), we examined the distribution of HLA-DRB1, DQA1, DQB1 loci in Mexican Mestizos of Central Mexico, using PCR-SSOP and PCR-SSP. Three groups were included: 47 type 2 diabetic ESRD patients; 42 patients with ESRD and 50 type 2 DM patients with no kidney complication. The results were compared with those of 101 controls of the same area. The median since DM was first diagnosed, was 18 years prior to the onset of ESRD. The frequencies of DRB1*1502 and DQB1*0501 were increased in DM patients with ESRD (p = 0.004; RR = 7.4, CI = 1.5-37; EF = 0. 13; p = 0.007; RR = 2.9, CI = 2.3-3.5, EF = 0.21, respectively). In contrast, DRB1*0407 was decreased in the same group (p = 0.0008, RR = 0.2; CI = 0.035-0.70, PF = 0.19). Diabetic patients with DRB1*1502 are 8.8 times more likely to develop ESRD, independently of the duration time of DM. DRB1*1502 contributes to the susceptibility to ESRD while DRB1*0407 is involved in protection. The residue at DRB1-74 differs in these alleles: DRB1*0407 has glutamic acid and DRB1*1502 has an alanine, suggesting that this substitution may be important for both, peptide anchoring and for presentation to the T cells.
Assuntos
Diabetes Mellitus Tipo 2/complicações , Etnicidade/genética , Genes MHC da Classe II , Predisposição Genética para Doença , Falência Renal Crônica/genética , Adulto , Idoso , Idoso de 80 Anos ou mais , Diabetes Mellitus Tipo 2/epidemiologia , Diabetes Mellitus Tipo 2/genética , Feminino , Humanos , Falência Renal Crônica/epidemiologia , Masculino , México/epidemiologia , Pessoa de Meia-Idade , Reação em Cadeia da Polimerase/métodosRESUMO
Vogt-Koyanagi-Harada's syndrome (VKH) is an autoimmune disease prevalent in Mongoloids with evident participation of HLA. The aim of this study was to identify the class II DNA sequences involved in the etiopathogenesis of VKH in Mexican Mestizos. This study included 46 VKH patients and 170 controls. 75% were females (mean age at onset of 33.5 years). The disease evolved to chronicity (68%) and 25% of the patients were unresponsive to corticotherapy. DNA typing of HLA-DRB1, DQA1 and DQB1 was done following the 12th International Histocompatibility protocols. VKH was strongly dependent of DRB1 gene; DRB1*04 was found in 78.2% of the patients vs. 50.6% of the controls (p = 0.001). No particular DRB*04 subtype was significantly increased, suggesting that residues E-9 V-11; H-13; H-33 and Y-37 shared by all DR4s are implicated in susceptibility to VKH. However DRB1*0101 (p = 0.009, OR = 4.2) was clearly associated. This allele shares the motif LLEQRRAAG located at position 67-74 and 86 of DRB1 with *0405 associated in Japanese. Two HLA associated mechanisms may be triggering the autoimmune phenomena. One involving critical polymorphic residues expressed in different alleles. Secondly, some peptides may anchor to the conserved residues leaving other sequences to bind to the T cell receptor.
Assuntos
Antígenos HLA-DQ/genética , Antígenos HLA-DR/genética , Síndrome Uveomeningoencefálica/genética , Adulto , Alelos , Feminino , Frequência do Gene , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ , Cadeias HLA-DRB1 , Humanos , Masculino , México , Síndrome Uveomeningoencefálica/etnologia , Síndrome Uveomeningoencefálica/imunologiaRESUMO
The purpose of the present study was to investigate the influence of nutrients and insulin on IGFs and their binding proteins (IGFBPs) during the fetal and neonatal periods of three rat populations: (a) rats undernourished by a 35% reduction in the diet from day 16 of gestation, (b) streptozotocin-induced diabetic rats from the same day, or 4 days after birth, and (c) control rats. Fetuses from the diabetic population showed a decrease in insulinemia at 19 and 21 days, along with an increase in glycemia at all stages. Neither glycemia nor insulinemia changed in the fetuses of undernourished mothers, but body weight was decreased at birth. Serum IGF-II decreased at 18 and 19 days of gestation in fetuses from undernourished mother, and increased at 18, 19 and 21 days in fetuses from diabetic mothers. Serum IGFBPs of low molecular weight (IGFBP-1 and IGFBP-2) increased in the three fetal populations studied, although no changes in serum IGFBPs were found from the effect of undernutrition or diabetes, but fetal liver IGFBP-1 mRNA expression was found to decreased in undernourished and diabetic animals as compared with controls. In neonatal rats, body weight, insulinemia and serum GH decreased in both undernourished and diabetic rats vs controls, while glycemia decreased in the undernourished and increased in the diabetic group. Serum IGF-II decreased only in diabetic rats and serum IGF-I decreased in both groups. The neonatal serum 30 kDa complex (IGFBP-1 and -2) also increased in undernutrition and diabetes parallel to the expression of mRNA. But, taken together, the changes in IGFBP peptide levels and liver mRNA expression strongly suggest that the 30 kDa complex seems to be composed mostly of IGFBP-1 in the diabetic group and of both IGFBP-1 and -2 in the undernourished animals. The studies of liver mRNA expression of IGFs and IGFBPs confirm the different metabolic control mechanism for the availability of IGFs by the IGFBPs, depending on the animal's maturity. The different adaptation shown by the diabetic neonatal population was confirmed by correlation studies between body weight, glycemia, insulinemia, IGF-I and IGFBPs. The different mechanism of adaptation in diabetic vs undernourished rats seems to be probably due to the decisive role played by hyperglycemia in the diabetic population, and also shows the crucial influence of nutritional status on IGFs and IGFBPs.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Fígado/metabolismo , Distúrbios Nutricionais/metabolismo , RNA Mensageiro/metabolismo , Somatomedinas/genética , Animais , Animais Recém-Nascidos/metabolismo , Glicemia/metabolismo , Western Blotting , Peso Corporal , Proteínas de Transporte/genética , Feminino , Feto/metabolismo , Hormônio do Crescimento/sangue , Inibidores do Crescimento/genética , Insulina/sangue , Proteínas de Ligação a Fator de Crescimento Semelhante a Insulina , Fator de Crescimento Insulin-Like I/análise , Fator de Crescimento Insulin-Like II/análise , Gravidez , Ratos , Ratos Wistar , Análise de RegressãoRESUMO
The influence of hypothalamic and pituitary type II 5'deiodinase (5'D-II) activities and T3 content on pituitary TSH content was investigated in streptozotocin (STZ)-induced diabetic rats (D). The results show, first, that hypothalamic and pituitary 5'D-II activities were lower in neonatal D rats versus control (C) rats, and the normal developmental pattern was altered. Secondly, when D and C rats were thyroidectomized (Tx) at 25 days of age (D+Tx, C+Tx), pituitary and hypothalamic 5'D-II activities increased ten days later in both populations vs. intact rats, but the percentage of increase was smaller in D+Tx than in C+Tx. The hypothalamic T3 to T4 ratios were also decreased in D+Tx animals (0.38) as compared to C+Tx rats (1.64). The hypothalamic T3 content was reduced by 30% in D as compared to C rats and by 80% in D+Tx as compared to C+Tx rats, showing a defect in hypothalamic T4 deiodination. Pituitary TSH content increased after Tx in D+Tx, but not in C+Tx. These results in diabetic rats indicate that the hypothalamic and pituitary 5'D-II activity and hypothalamic T3 content are affected by diabetes and play a role in the regulation of pituitary TSH content.
Assuntos
Diabetes Mellitus Experimental/metabolismo , Iodeto Peroxidase/metabolismo , Tireotropina/metabolismo , Tri-Iodotironina/metabolismo , Animais , Diabetes Mellitus Experimental/induzido quimicamente , Diabetes Mellitus Experimental/enzimologia , Modelos Animais de Doenças , Hipotálamo/enzimologia , Hipotálamo/metabolismo , Hipófise/enzimologia , Hipófise/metabolismo , Ratos , Ratos Wistar , Estreptozocina , Tireoidectomia , Iodotironina Desiodinase Tipo IIRESUMO
Type I diabetes is an autoimmune and a polygenic disease, in which MHC-class II genes contribute to 48% of the disease. The aim of the present study, is to provide a guideline to understanding the molecular association of these genes, through the immunogenetic analysis of 3 Latin american mestizo populations. We included 606 individuals, 349 patients with DMDI and 257 healthy controls coming from 3 geographical areas: Mexico City, Mexico; Caracas, Venezuela and Medellin, Colombia. The results clearly indicate that in mestizo groups, the diabetogenic haplotypes are from mediterranean ancestry, while protection is due to Amerindian genes. It was demonstrated that the relevant sequences for IDDM expression are located to DRB1 and DQB1 loci with a minimal contribution of DQA1 residues. The sequences determining peptide recognition and the induction of TH1 cells mediating the cellular autoimmune response are in positions DRB1-57 and 74 (an aspartic acid and a glutamic acid respectively, confer protection), modulated by D-57 in the DQ, 8 chain. These data show that DRB1-DQB1 haplotypes are central for IDDM expression and open new pathways for the disease management.
Assuntos
Doenças Autoimunes/epidemiologia , Diabetes Mellitus Tipo 1/epidemiologia , Genes MHC da Classe II , Adolescente , Adulto , Idade de Início , Ásia/etnologia , Doenças Autoimunes/etnologia , Doenças Autoimunes/genética , Criança , Pré-Escolar , Colômbia/epidemiologia , Diabetes Mellitus Tipo 1/etnologia , Diabetes Mellitus Tipo 1/genética , Suscetibilidade a Doenças , Etnicidade/genética , Europa (Continente)/etnologia , Feminino , Genótipo , Antígenos HLA-DQ/genética , Cadeias alfa de HLA-DQ , Cadeias beta de HLA-DQ , Antígenos HLA-DR/genética , Cadeias HLA-DRB1 , Haplótipos , Humanos , Indígenas Norte-Americanos , Indígenas Sul-Americanos , Lactente , América Latina/epidemiologia , Masculino , México/epidemiologia , Fatores de Risco , Venezuela/epidemiologia , População BrancaRESUMO
Understanding the complex interaction between human leukocyte antigen (HLA) and killer immunoglobulin-like receptor (KIR) requires study of both HLA and KIR diversity in the same population. The presence of KIR genes 2DL1, 2, 3, 4, 5, KIR3DL1, 3DL2, 3DL3, KIR2DS1, 2DS2, 2DS3, 2DS4, 2DS5, KIR3DS1, KIR3DP1, KIR2DP1 was determined in 54 unrelated Mexican Mestizo donors. The PCR sequence-specific oligonucleotide probe One Lambda kit (Luminex) kindly given by J. Lee was used for typing. The software analyses the combination obtained for each of the five exons. Five controls (UCLA DNA exchange) were run as quality control. The gene frequency (GF) was calculated for the 16 KIR loci; the GF of individual genes was 100% for 2DL4, 3DL1, 3DL2, 3DL3, 3DP1. KIR2DL1 (76.43%), KIR2DL2 (37.64%), KIR2DL3 (76.43%), KIR2DL5 (29.29%), KIR3DS1 (23.02%), KIR2DS1 (21.83%), KIR2DS2 (37.64%), KIR2DS3 (50.93%), KIR2DS4 (86.93%), KIR2DS5 (29.29%), KIR2DP1 (86.39%). We observed similar frequencies with Caucasians and Mediterraneans, with exceptions: KIR3DL1 which was present in 100% Mexicans, ranged from 62% to 75% in Caucasians; 2DS3 (50.9%) vs 14-20% 2DS4 (86.39%) vs 65-79% and 2DS5 (29.29%) vs 11-18% in Caucasians. The finding of 23 phenotypes in 54 individuals accounting for both chromosomes, demonstrates the enormous diversity. We found 14 different combinations of stimulatory KIRs in the phenotypes; every subject had at least one stimulatory KIR; in all of them, 2DS4 existed except for one person who may have some new combination: 2DS2 2DS3. Extended family data will offer accurate and precise haplotypes to provide an insight on the significance of ethnic distribution and KIR repertoire.
Assuntos
Etnicidade/genética , Células Matadoras Naturais/imunologia , Polimorfismo Genético , Receptores Imunológicos/genética , Frequência do Gene , Genética Populacional , Genótipo , Haplótipos , Humanos , México/etnologia , Fenótipo , Receptores Imunológicos/classificação , Receptores Imunológicos/imunologia , Receptores KIR , Receptores KIR2DL1 , Receptores KIR2DL2 , Receptores KIR2DL3 , Receptores KIR2DL4 , Receptores KIR3DL1 , Receptores KIR3DL2 , Receptores KIR3DS1RESUMO
The direct involvement of the human leukocyte antigen class II DR-DQ genes in type 1 diabetes (T1D) is well established, and these genes display a complex hierarchy of risk effects at the genotype and haplotype levels. We investigated, using data from 38 studies, whether the DR-DQ haplotypes and genotypes show the same relative predispositional effects across populations and ethnic groups. Significant differences in risk within a population were considered, as well as comparisons across populations using the patient/control (P/C) ratio. Within a population, the ratio of the P/C ratios for two different genotypes or haplotypes is a function only of the absolute penetrance values, allowing ranking of risk effects. Categories of consistent predisposing, intermediate ('neutral'), and protective haplotypes were identified and found to correlate with disease prevalence and the marked ethnic differences in DRB1-DQB1 frequencies. Specific effects were identified, for example for predisposing haplotypes, there was a statistically significant and consistent hierarchy for DR4 DQB1*0302s: DRB1*0405 =*0401 =*0402 > *0404 > *0403, with DRB1*0301 DQB1*0200 (DR3) being significantly less predisposing than DRB1*0402 and more than DRB1*0404. The predisposing DRB1*0401 DQB1*0302 haplotype was relatively increased compared with the protective haplotype DRB1*0401 DQB1*0301 in heterozygotes with DR3 compared with heterozygotes with DRB1*0101 DQB1*0501 (DR1). Our results show that meta-analyses and use of the P/C ratio and rankings thereof can be valuable in determining T1D risk factors at the haplotype and amino acid residue levels.