RESUMO
Chitotriosidase (CHIT, EC 3.2.1.14) is an enzyme secreted by activated macrophages with the ability to hydrolyze the chitin of pathogens. The high activity of this enzyme has been used as a secondary biomarker of response to treatment in patients with Gaucher disease (OMIM 230800). Within the world's population, approximately 6% is homozygous and 35% is heterozygous for the most common polymorphism in the CHIT1 gene, a 24-bp duplication (dup-24 bp), with homozygosity of this duplication causing inactivation of the enzyme but without major consequences for health. To determine the frequency of the dup-24 bp CHIT1 gene in indigenous populations from Mexico, 692 samples were analyzed: Purepecha (49), Tarahumara (97), Huichol (97), Mayan (139), Tenek (97), and Nahua (213). We found that the groups were in Hardy-Weinberg equilibrium. The dup-24 bp allele frequency was found to be (in order of highest to lowest) 37% (Mayan), 34% (Huichol and Nahua), 33% (Purepecha), 31% (Tenek), and 29% (Tarahumara).
RESUMO
Polymorphisms in the CAMP gene (cathelicidin) have not been tested in tuberculosis susceptibility. We tested polymorphisms rs9844812 (HIF-1α::ARNT binding site) and rs56122065 (CAMP) plus rs1800972 (DEFB1). SNP rs1800972 was associated with extrapulmonary tuberculosis (EPTB) in a codominant model (genotype CG, P = 0.037, OR 4.82; 95% CI: 0.92-47.42; statistical power, 82%), but not PTB (P = 0.101) in a Mexican population.
Assuntos
Peptídeos Catiônicos Antimicrobianos/genética , Predisposição Genética para Doença , Subunidade alfa do Fator 1 Induzível por Hipóxia/genética , Polimorfismo Genético , Tuberculose/genética , Regiões 5' não Traduzidas , Alelos , Sequência de Aminoácidos , Peptídeos Catiônicos Antimicrobianos/química , Translocador Nuclear Receptor Aril Hidrocarboneto/genética , Translocador Nuclear Receptor Aril Hidrocarboneto/metabolismo , Sequência de Bases , Sítios de Ligação , Estudos de Casos e Controles , Éxons , Frequência do Gene , Genótipo , Humanos , Subunidade alfa do Fator 1 Induzível por Hipóxia/metabolismo , Dados de Sequência Molecular , Motivos de Nucleotídeos , Polimorfismo de Nucleotídeo Único , Matrizes de Pontuação de Posição Específica , Regiões Promotoras Genéticas , Ligação Proteica , Tuberculose/metabolismo , Tuberculose Pulmonar/genética , Tuberculose Pulmonar/metabolismo , beta-Defensinas/genética , CatelicidinasRESUMO
Rheumatoid arthritis (RA) is the prototype of the rheumatic diseases worldwide. Methotrexate (MTX) is the drug of first choice in the treatment of this disease due to its immunosuppressant effect. However, side events are present in 30% of the patients. The C677T and A1298C polymorphisms of the methylenetetrahydrofolate reductase (MTHFR) gene are involved in the metabolism of MTX. Earlier studies reported an association between these polymorphisms and elevation of hepatic enzymes. We analyzed the frequencies of both polymorphisms and the presence of transaminasemia in 70 Mexican patients with rheumatic arthritis treated with MTX. The 19% (13/70) of patients had an increase in the serum level of transaminases. The A1298C polymorphism was associated with elevation of transaminases (P=0.024). The identification of MTHFR genotypes for C677T and A1298C polymorphisms could lead clinicians to identify patients in risk of elevation of transaminases, and give them an individualized treatment, as is a goal of pharmacogenetics.
Assuntos
Antirreumáticos/efeitos adversos , Artrite Reumatoide/tratamento farmacológico , Artrite Reumatoide/genética , Metotrexato/efeitos adversos , Metilenotetra-Hidrofolato Redutase (NADPH2)/genética , Polimorfismo Genético , Transaminases/sangue , Antirreumáticos/farmacocinética , Artrite Reumatoide/enzimologia , Artrite Reumatoide/etnologia , Estudos de Casos e Controles , Distribuição de Qui-Quadrado , Frequência do Gene , Genótipo , Humanos , Metotrexato/farmacocinética , Metilenotetra-Hidrofolato Redutase (NADPH2)/metabolismo , México/epidemiologia , Razão de Chances , Farmacogenética , Fenótipo , Medicina de Precisão , Medição de Risco , Fatores de Risco , Resultado do Tratamento , Regulação para CimaRESUMO
We describe for the first time the high-resolution profiling of HLA-A, -B, -C, -DRB1, -DQB1 and -DPB1 in a culturally and geographically distinct Mexican ethnic group, the Tarahumaras. The alleles most frequently found by reference strand-mediated conformational analysis in this population were for class I: HLA-A*240201, *020101/09, *0206, *310102, *680102; HLA-B*4002, *1501, *510201, *3501/02/03, *4005, *4801; HLA-Cw*0304, *0801, *0102, *040101; and for class II: HLA-DRB1*080201, *1402, *040701; HLA-DQB1*0402, *0301, *0302/07; HLA-DPB1*0402, *0401, *020102. In addition, a novel allele, HLA-A*0257, was found. Based on comparison of presently known HLA-DRB1 and -DQB1 allele frequencies in Amerindian groups and worldwide populations, the Tarahumaras are unexpectedly more related to the geographically and linguistically distant Aymara and Terena Amerindian groups than they are to neighbouring tribes.
Assuntos
Genes MHC da Classe II , Genes MHC Classe I , Indígenas Norte-Americanos/genética , Filogenia , Etnicidade/genética , Geografia , Haplótipos , Análise Heteroduplex , Humanos , Idioma , México , Polimorfismo GenéticoRESUMO
We studied six Y-linked short tandem repeats (Y-STRs) to describe the internal diversity of the Amerindian haplogroup Q-M3 in 129 males from eight Mexican populations. The low gene diversity in the Huichol tribe demonstrated the effects of genetic drift, attributable to geographic isolation and founder effect. The presence of two principal paternal lineages supported the historical and anthropometric records, which indicate that Huichols were formed by the fusion of two ancestral Mexican tribes. Moreover, genetic distances and close relationships of haplotypes between Huichols and Tarahumaras were in agreement with their linguistic affiliation. The high genetic diversity of the Purépechas and wide distribution of haplotypes along the constructed network-joining tree suggest that the present genetic composition was influenced by Purépecha dominance in western Mesoamerica. The Y-haplotypes shared between populations suggest that, among the Amerindian tribes studied herein, the paternal genetic pool of Nahuas could have contributed more importantly to the European-admixed population, the Mexican-Mestizos.
Assuntos
Cromossomos Humanos Y , Etnicidade/genética , Genética Populacional , Haplótipos , Impressões Digitais de DNA , Frequência do Gene , Humanos , Masculino , México , Sequências de Repetição em TandemRESUMO
Killer cell immunoglobulin-like receptors are characterized by their great diversity of genes and alleles. Population studies have identified the presence of a broad variety of genotypes. In Mexico, there are diverse ethnic groups representing 9% of the total population and the rest is composed of Mestizos with a more varied biology. For the purpose of this study, genotyping was performed in Mestizos, in Mexico City inhabitants, and in three ethnic groups. The frequencies of genes KIR2DL2, 2DL5, 2DS1-3, 2DS5, and 3DS1 showed a greater variability in the groups studied. A total of 12 different genotypes were identified, the higher number for the Mestizos and the lower number for the Tarahumaras. Genotype 1 was found at a greater frequency in all the groups, except for the Tarahumaras, in which genotype 4 was more frequent. The frequency of genotypes 4 and 8 in Mexicans was higher than that for other populations analyzed. By subtyping of KIR3DL1, 3DL2, 2DL1, and 2DL3, two B haplotypes were identified in families; both were absent in Caucasian families. Our results indicated a greater diversity of genes in the Mestizos group than in the ethnic groups.
Assuntos
Indígena Americano ou Nativo do Alasca/genética , Etnicidade/genética , Receptores Imunológicos/genética , Frequência do Gene , Variação Genética , Genótipo , Haplótipos , Humanos , Desequilíbrio de Ligação , México/etnologia , População/genética , Receptores KIR , Receptores KIR2DL1 , Receptores KIR2DL2 , Receptores KIR2DL3 , Receptores KIR3DL1 , Receptores KIR3DL2 , Receptores KIR3DS1RESUMO
BACKGROUND: The frequency of haplotypes of Nsp I-Eco47 III sites, at the IDUA (alpha-L iduronidase) gene, in Huichol, Tarahumara and Mestizo Mexican population is reported. METHODS: Eco47 III and Nsp I intragenic polymorphisms in IDUA gene are studied in three (Mestizo, Huichol and Tarahumara populations) Mexican groups. Data from normal Australian [Hum. Genet. 90 (1992) 327] individuals were considered for comparative analyses. RESULTS: The genotypes for IDUA Eco47 III and Nsp I sites in Mexicans were in agreement with Hardy-Weinberg equilibrium. Allele frequency distributions for individual sites differed (P < 0.05) except at site B1 in the Huichol group. Haplotype Eco47 III-Nsp I frequency distributions were different in the three Mexican normal groups, and it was also observed when to compared with the normal Australians. CONCLUSIONS: This characteristic makes the two IDUA polymorphic sites useful for identification purposes, and these polymorphisms could be included in a PCR based battery of DNA markers.
Assuntos
Desoxirribonucleases de Sítio Específico do Tipo II/genética , Frequência do Gene , Iduronidase/genética , Polimorfismo de Fragmento de Restrição , Adulto , Haplótipos , Humanos , México/etnologiaRESUMO
BACKGROUND: Short tandem repeats (STRs) on the non-pseudoautosomal region of the Y-chromosome are DNA polymorphic markers able to solve special cases in legal medicine, for instance in paternity testing where the alleged father is not available, and in forensic situations, such as rape cases, where mixtures of male/female DNA are present. METHODS: Six STR polymorphisms from the Y-chromosome (DYS19, DYS385, DYS389/I, DYS390, DYS391, and DYS393) were PCR-typed in 120 males from the northwest region of Mexico by means of native polyacrylamide gel electrophoresis and silver staining. RESULTS: Allele frequencies were estimated for each STR. Their gene diversity ranged from 51.4% for DYS393 to 92.5% for DYS385. Mexican Y-STR allele distributions displayed similarity (p >0.05) with previously reported U.S. Hispanics for DYS19, DYS389/I, DYS390, DYS391, and DYS393. Although Mexicans showed the same modal allele for DYS385 (11/14; 24.4%) with regard to most European populations, differences in allele distributions were observed (p <0.01). The haplotype diversity and the male discriminatory capacity of this six-locus system were 99.3 and 84.1%, respectively. CONCLUSIONS: This knowledge permits the effective use of these six Y-chromosome markers in legal medicine casework in the studied population. This STR-system offers a great potential to identify males and male-lineages, and can be used confidentially in paternity testing and forensic analysis in the Mexican population.
Assuntos
Genética Populacional , Haplótipos , Sequências de Repetição em Tandem , Cromossomo Y , Sequência de Bases , Primers do DNA , Eletroforese em Gel de Poliacrilamida , Humanos , Masculino , MéxicoRESUMO
BACKGROUND: Short tandem repeats or STRs on the non-pseudoautosomal region of the Y-chromosome are polymorphic markers used to obtain a specific male DNA profile to unravel special cases in the Legal Medicine casework. Haplotypes of Y-chromosome are constructed by analysis of many STRs. They allow solving paternity cases where the alleged father is not available, as well as forensic situations, as rape cases, where mixtures of male/female DNA are present. METHODS: Five Y-linked STRs recently informed: A4, A7.1, A7.2, A10 y C4 (White et al. 1999) were PCR-typed in 101 mexican mestizos from the Northwest of Mexico by means of native polyacrilamide gel electrophoresis and silver staining. RESULTS: Allelic frequencies were estimated for each STR. Their gene diversity ranged from 57.1% for A-4 to 74.7% for C-4. Excepting for A-4, Mexican Y-chromosome STR allele distributions displayed similarity (p > 0.05) to the previously informed population. Seventy-five different haplotypes were observed from 98 complete haplotypes obtained. The haplotype diversity and the male discriminatory capacity of this five-locus system were 99.0% and 77.5%, respectively. CONCLUSIONS: This knowledge permits to use effectively these five Y-chromosome markers in legal medicine casework in the studied population. This STR-system is a new resource of Y-chromosome polymorphism that offers a great potential to identify males and male-lineages, and can be used confidentially in paternity testing and forensic analysis in Mexican population.
Assuntos
Repetições de Microssatélites , Cromossomo Y/genética , Adulto , Alelos , DNA/genética , Eletroforese em Gel de Poliacrilamida , Medicina Legal/métodos , Variação Genética , Haplótipos/genética , Humanos , México , Paternidade , Reação em Cadeia da PolimeraseRESUMO
The apoptotic index (AI) of peripheral blood lymphocytes (PBL) and plasma corticosterone (CS) levels were determined in Wistar rats treated with phenytoin (PHT) at therapeutic and toxic doses (100 or 200 mg/kg/day, respectively, over a period of 7 days) and stressed by bifrontal electric shock (60 Hz/40 mA/0.2 seg). The values of CS and AI were found to be significantly higher in rats submitted to electric shock (ES) and in rats treated with therapeutic and toxic doses of PHT plus ES, than in rats treated only with PHT (P<0.001). The plasma concentrations of PHT were found to be significantly higher in rats treated with toxic doses than in those treated with therapeutic doses (P<0.001), while the control group (without treatment) and vehicle group (propilenglycol-ethanol-water, 40:10:50), showed low levels of CS, and less than 1% of AI. The DNA analysis by electrophoresis in agarose in all the groups was positive, displaying the ladder pattern characteristic of apoptotic process (200 bp), except in the control groups (no treatment and vehicle treated). Our results demonstrate that chronic stress, caused by ES, produces an elevation of CS. The values of apoptosis were correlated with the CS levels, suggesting that the apoptotic inductor process is a consequence of an increase in the concentration of corticosterone in plasma, in response to the hypothalamic-pituitary-adrenals (HPA) axis activation, while phenytoin at therapeutic doses is only a moderate apoptosis inductor.