RESUMEN

Even though immunoglobulins are critical for immune responses and human survival, the diversity of the immunoglobulin heavy chain gene (IGH) is poorly known and mostly characterized only by serological methods. Moreover, this genomic region is not well-covered in genomic databases and genome-wide association studies due to particularities that impose technical difficulties for its analysis. Therefore, the IGH gene has never been systematically sequenced across populations. Here, we deliver an unprecedented and comprehensive characterization of the diversity of the IGHG1, IGHG2, and IGHG3 gene segments, which encode the constant region of the most abundant circulating immunoglobulins: IgG1, IgG2, and IgG3, respectively. We used Sanger sequencing to analyze 357 individuals from seven different Brazilian populations, including five Amerindian, one Japanese-descendant and one Euro-descendant population samples. We discovered 28 novel IGHG alleles and provided evidence that some of them may have been originated by gene conversion between common alleles of different gene segments. The rate of synonymous substitutions was significantly higher than the rate of the non-synonymous substitutions for IGHG1 and IGHG2 (p = 0.01 and 0.03, respectively), consistent with purifying selection. Fay and Wu's test showed significant negative values for most populations (p < 0.001), which indicates that positive selection in an adjacent position may be shaping IGHG variation by hitchhiking of variants in the vicinity, possibly the regions that encode the Ig variable regions. This study shows that the variation in the IGH gene is largely underestimated. Therefore, exploring its nucleotide diversity in populations may provide valuable information for comprehension of its evolution, its impact on diseases and vaccine research.

Asunto(s)

Alelos , Conversión Génica , Genes de las Cadenas Pesadas de las Inmunoglobulinas , Variación Genética , Genética de Población , Cadenas gamma de Inmunoglobulina/genética , Selección Genética , Brasil/epidemiología , Frecuencia de los Genes , Geografía , Haplotipos , Humanos , Alotipos de Inmunoglobulina Gm/genética , Desequilibrio de Ligamiento , Polimorfismo de Nucleótido Simple

RESUMEN

Glycoprotein-A repetitions predominant (GARP) is a transmembrane protein that is highly expressed in breast cancer. Its overexpression correlates with worse survival, and antibodies to GARP appear to play a protective role in a mouse model. No large-scale studies of immunity to GARP in humans have yet been undertaken. In this investigation, using a large multiethnic cohort (1738 subjects), we aimed to determine whether the magnitude of anti-GARP antibody responsiveness was significantly different in patients with breast cancer from that in matched healthy controls. We also investigated whether the allelic variation at the immunoglobulin GM (γ marker), KM (κ marker), and Fcγ receptor (FcγR) loci contributed to the interindividual variability in anti-GARP IgG antibody levels. A combined analysis of all subjects showed that levels of anti-GARP antibodies were significantly higher in patients with breast cancer than in healthy controls (mean ±â€¯SD: 7.4 ±â€¯3.5 vs. 6.9 ±â€¯3.5 absorbance units per mL (AU/µL), p < 0.0001). In the two populations with the largest sample size, the probability of breast cancer generally increases as anti-GARP antibody levels increase. Several significant individual and epistatic effects of GM, KM, and FcγR genotypes on anti-GARP antibody responsiveness were noted in both patients and controls. These results, if confirmed by independent investigations, will aid in devising personalized GARP-based immunotherapeutic strategies against breast cancer and other GARP-overexpressing malignancies.

Asunto(s)

Neoplasias de la Mama/genética , Genotipo , Alotipos de Inmunoglobulina Gm/genética , Alotipos Km de Inmunoglobulina/genética , Inmunoterapia/métodos , Proteínas de la Membrana/inmunología , Receptores de IgG/genética , Formación de Anticuerpos , Brasil , Neoplasias de la Mama/inmunología , Estudios de Casos y Controles , Estudios de Cohortes , Epistasis Genética , Etnicidad , Femenino , Humanos , Inmunoglobulina G/sangre , Proteínas de la Membrana/genética , Polimorfismo Genético , Medicina de Precisión

RESUMEN

Tumour-associated antigen human epidermal growth factor receptor 2 (HER2) is over-expressed in 25-30% of breast cancer patients and is associated with poor prognosis. Naturally occurring anti-HER2 antibody responses have been described in patients with HER2 over-expressing tumours. There is significant interindividual variability in antibody responsiveness, but the host genetic factors responsible for this variability are poorly understood. The aim of the present investigation was to determine whether immunoglobulin genetic markers [GM (genetic determinants of γ chains)] and Fcγ receptor (FcγR) alleles contribute to the magnitude of natural antibody responsiveness to HER2 in patients with breast cancer. A total of 855 breast cancer patients from Japan and Brazil were genotyped for several GM and FcγR alleles. They were also characterized for immunoglobulin (Ig)G antibodies to HER2. In white subjects (n = 263), GM 23-carriers had higher levels of anti-HER2 antibodies than non-carriers of this allele (p = 0·004). At the GM 5/21 locus, the homozygotes for the GM 5 allele had higher levels of anti-HER2 antibodies than the other two genotypes (P = 0·0067). In black subjects (n = 42), FcγRIIa-histidine/histidine homozygotes and FcγRIIIa-phenylalanine/valine heterozygotes were associated with high antibody responses (P = 0·0071 and 0·0275, respectively). FcγR genotypes in white subjects and GM genotypes in black subjects were not associated with anti-HER2 antibody responses. No significant associations were found in other study groups. These racially restricted contributions of GM and FcγR genotypes to humoral immunity to HER2 have potential implications for immunotherapy of breast cancer.

Asunto(s)

Neoplasias de la Mama/genética , Neoplasias de la Mama/inmunología , Inmunidad Humoral/genética , Alotipos de Inmunoglobulina Gm/genética , Grupos Raciales/genética , Receptor ErbB-2/inmunología , Receptores de IgG/genética , Alelos , Pueblo Asiatico/genética , Población Negra/genética , Brasil , Neoplasias de la Mama/terapia , Femenino , Genotipo , Humanos , Inmunoterapia , Japón , Población Blanca/genética

RESUMEN

BACKGROUND: Humoral immune responses play a key role in the development of immunity to malaria, but the host genetic factors that contribute to the naturally occurring immune responses to malarial antigens are not completely understood. The aim of the present investigation was to determine whether, in subjects exposed to malaria, GM and KM allotypes--genetic markers of immunoglobulin gamma and kappa-type light chains, respectively--contribute to the magnitude of natural antibody responses to target antigens that are leading vaccine candidates for protection against Plasmodium vivax. METHODS: Sera from 210 adults, who had been exposed to malaria transmission in the Brazilian Amazon endemic area, were allotyped for several GM and KM determinants by a standard hemagglutination-inhibition method. IgG subclass antibodies to P. vivax apical membrane antigen 1 (PvAMA-1) and merozoite surface protein 1 (PvMSP1-19) were determined by an enzyme-linked immunosorbent assay. Multiple linear regression models and the non-parametric Mann-Whitney test were used for data analyses. RESULTS: IgG1 antibody levels to both PvMSP1-19 and PvAMA-1 antigens were significantly higher (P = 0.004, P = 0.002, respectively) in subjects with the GM 3 23 5,13,14 phenotype than in those who lacked this phenotype. CONCLUSIONS: Results presented here show that immunoglobulin GM allotypes contribute to the natural antibody responses to P. vivax malaria antigens. These findings have important implications for the effectiveness of vaccines containing PvAMA-1 or PvMSP1-19 antigens. They also shed light on the possible role of malaria as one of the evolutionary selective forces that may have contributed to the maintenance of the extensive polymorphism at the GM loci.

Asunto(s)

Anticuerpos Antiprotozoarios/inmunología , Antígenos de Protozoos/inmunología , Inmunoglobulina G/inmunología , Malaria Vivax/inmunología , Plasmodium vivax/inmunología , Adulto , Anticuerpos Antiprotozoarios/sangre , Antígenos de Protozoos/genética , Brasil , Ensayo de Inmunoadsorción Enzimática , Femenino , Marcadores Genéticos , Humanos , Inmunoglobulina G/sangre , Alotipos de Inmunoglobulina Gm/genética , Alotipos de Inmunoglobulina Gm/inmunología , Alotipos Km de Inmunoglobulina/genética , Alotipos Km de Inmunoglobulina/inmunología , Modelos Lineales , Vacunas contra la Malaria/inmunología , Malaria Vivax/prevención & control , Masculino , Proteínas de la Membrana/inmunología , Proteína 1 de Superficie de Merozoito/inmunología , Persona de Mediana Edad , Fenotipo , Plasmodium vivax/genética , Proteínas Protozoarias/inmunología , Estadísticas no Paramétricas , Adulto Joven

RESUMEN

The Noir Marron communities are the direct descendants of African slaves brought to the Guianas during the four centuries (16th to 19th) of the Atlantic slave trade. Among them, three major ethnic groups have been studied: the Aluku, the Ndjuka and the Saramaka. Their history led them to share close relationships with Europeans and Amerindians, as largely documented in their cultural records. The study of Gm polymorphisms of immunoglobulins may help to estimate the amount of gene flow linked to these cultural exchanges. Surprisingly, very low levels of European contribution (2.6%) and Amerindian contribution (1.7%) are detected in the Noir Marron gene pool. On the other hand, an African contribution of 95.7% redraws their origin to West Africa (F(ST) < or = 0.15). This highly preserved African gene pool of the Noir Marron is unique in comparison to other African American populations of Latin America, who are notably more admixed.

Asunto(s)

Población Negra/genética , Etnicidad/genética , Variación Genética , Alotipos de Inmunoglobulina Gm/genética , África Occidental/etnología , Consanguinidad , Características Culturales , Europa (Continente)/etnología , Femenino , Efecto Fundador , Guyana Francesa , Haplotipos/genética , Humanos , Indígenas Sudamericanos/genética , Masculino , Matrimonio , Población Blanca/genética

RESUMEN

We analyzed the natural killer cell immunoglobulin-like receptor (KIR) genes and immunoglobulin allotypes in the development of type 2 diabetes (T2D) based on body mass index (BMI) measurements (obese vs. non-obese) in Puerto Rican Americans. Genetic interactions between the KIR haplotype A homozygotes (HAH) and its fraction containing two inhibitory receptors 2DL3 and 2DL1 and the activating receptor 2DS4 with immunoglobulin allotypes were studied. We found a significant association between the HAH and T2D (p=0.002; OR=7.97) and its interaction with the immunoglobulin allotype z: GM f/f (-) (p=<0.0001; OR, not determined) only in non-obese individuals. This association were due to the interactions between the 2DL3/2DL3, 2DL1/2DL1, and 2DS4 fragment with GM f/f (-) in T2D patients (p=0.0017; OR=3.45). Analysis based on BMI demonstrated associations in both obese (p=0.037; OR=2.43; 95% CI=0.97-6.31) and non-obese individuals (p=<0.0001; OR=8.38; 95% CI=2.49-29.31). By contrast, the interaction of the GM allotype f/f (-) with the HAH fragment was associated with T2D only in non-obese individuals (p=<0.0001; OR=18.2; 95% CI=3.71-113.4). As expected, interaction of both HAH and its fragment with HLA-C group's ligands were significant. We used informative short tandem repeats (STRs) that distinguish major populations to determine genetic admixture and found that there was no genetic stratification in our cohort. Our findings are consistent with the possibility of an autoimmune and/or innateimmune component in the pathogenesis of T2D: NK receptors with chronic inflammation in obese and genetic interactions with G1M allotype in T2D non-obese possibly mediating autoimmunity.

Asunto(s)

Diabetes Mellitus Tipo 2/genética , Alotipos de Inmunoglobulinas/genética , Alotipos de Inmunoglobulina Gm/genética , Obesidad/genética , Receptores KIR/genética , Anciano , Índice de Masa Corporal , Estudios de Casos y Controles , Diabetes Mellitus Tipo 2/etnología , Femenino , Haplotipos , Hispánicos o Latinos/genética , Homocigoto , Humanos , Células Asesinas Naturales/inmunología , Masculino , Persona de Mediana Edad , Proteínas de Unión al GTP Monoméricas , Puerto Rico/etnología , Receptores KIR/análisis , Estados Unidos

RESUMEN

OBJECTIVE: As part of a larger, worldwide study of the ethnogeography of myositis, we evaluated the clinical, serologic, and immunogenetic features of Mestizo (Mexican and Guatemalan) and North American Caucasian patients with idiopathic inflammatory myopathy (IIM). METHODS: Clinical manifestations, autoantibodies, HLA-DRB1 and DQA1 alleles, and immunoglobulin Gm/Km allotypes were compared between 138 Mestizos with IIM and 287 Caucasians with IIM, using the same classification criteria and standardized questionnaires. RESULTS: IIM in Mestizo patients was characterized by a higher proportion of dermatomyositis (69% of adult Mestizos versus 35% of adult Caucasians; P < 0.001) and anti-Mi-2 autoantibodies (30% versus 7% of adults, respectively, and 32% versus 4% of children, respectively; P < 0.01). Genetic risk factors also differed in these populations. Whereas Mestizos had no HLA risk factors for IIM, HLA-DRB1*0301, the linked allele DQA1*0501, and DRB1 alleles sharing the first hypervariable region motif (9)EYSTS(13) were major risk factors in Caucasian patients with IIM. Furthermore, different HLA-DRB1 and DQA1 alleles were associated with anti-Mi-2 autoantibodies (DRB1*04 and DQA1*03 in Mestizos and DRB1*07 and DQA1*02 in Caucasians). Immunoglobulin gamma-chain allotypes Gm(1), Gm(17) (odds ratio for both 11.3, P = 0.008), and Gm(21) (odds ratio 7.3, P = 0.005) and kappa-chain allotype Km(3) (odds ratio 7.3, P = 0.005) were risk factors for IIM in Mestizos; however, no Gm or Km allotypes were risk or protective factors in Caucasians. In addition, Gm and Km phenotypes were unique risk factors (Gm 1,3,17 5,13,21 and Gm 1,17 23 21 and Km 3,3) or protective factors (Km 1,1) for the development of myositis and anti-Mi-2 autoantibodies (Gm 1,2,3,17 23 5,13,21) in adult Mestizos. CONCLUSION: IIM in Mesoamerican Mestizos differs from IIM in North American Caucasians in the frequency of phenotypic features and in the immune-response genes predisposing to and protecting from myositis and anti-Mi-2 autoantibodies at 4 chromosomal loci. These and other data suggest the likelihood that the expression of IIM is modulated by different genes and environmental exposures around the world.

Asunto(s)

Miositis/epidemiología , Adulto , Alelos , Dermatomiositis/epidemiología , Dermatomiositis/genética , Dermatomiositis/inmunología , Femenino , Genotipo , Guatemala/epidemiología , Antígenos HLA-DQ/análisis , Cadenas alfa de HLA-DQ , Antígenos HLA-DR/análisis , Cadenas HLA-DRB1 , Humanos , Alotipos de Inmunoglobulina Gm/análisis , Región de Unión de la Inmunoglobulina , Indígenas Centroamericanos , Masculino , México/epidemiología , Miositis/genética , Miositis/inmunología , Fenotipo , Factores de Riesgo , Estados Unidos/epidemiología

RESUMEN

Vaccine development is one of the most promising and exciting fields in cancer research; numerous approaches are being studied to developed effective cancer vaccines. The aim of this form of therapy is to teach the patient's immune system to recognize the antigens expressed in tumor cells, but not in normal tissue, to be able to destroy these abnormal cells leaving the normal cells intact. In other words, is an attempt to teach the immune system to recognize antigens that escaped the immunologic surveillance and are by it, therefore able to survive and, in time, disseminate. However each research group developing a cancer vaccine, uses a different technology, targeting different antigens, combining different carriers and adjuvants, and using different immunization schedules. Most of the vaccines are still experimental and not approved by the US or European Regulatory Agencies. In this work, we will offer an update in the knowledge in cancer immunology and all the anticancer vaccine approaches, with special emphasis in ganglioside based vaccines. It has been demonstrated that quantitative and qualitative changes occur in ganglioside expression during the oncogenic transformation. Malignant transformation appears to activate enzymes associated with ganglioside glycosylation, resulting in altered patterns of ganglioside expression in tumors. Direct evidence of the importance of gangliosides as potential targets for active immunotherapy has been suggested by the observation that human monoclonal antibodies against these glycolipids induce shrinkage of human cutaneous melanoma metastasis. Thus, the cellular over-expression and shedding of gangliosides into the interstitial space may play a central role in cell growth regulation, immune tolerance and tumor-angiogenesis, therefore representing a new target for anticancer therapy. Since 1993 researchers at the University of Buenos Aires and the University of Quilmes (Argentina), have taken part in a project carried out by the (CIM) from La Havana, Cuba, to developed new strategies for specific active immunotherapy. The project included two ganglioside based vaccines and one anti-idiotypic vaccine. We focused on two antigens: first GM3, an ubiquitous antigen which is over-expressed in several epithelial tumor types; and a second one, N-Glycolyl-GM3 a more molecule, not being expressed in normal tissues and recently found in several neoplastic cells, in particular breast, melanoma and neuroectodermal cancer cells. We developed two vaccines, one with each antigen, both using proteins derived from the outer membrane proteins (OMP) of Neisseria Meningitidis B, as carriers. We developed also the 1E10 vaccine; an anti-idiotype vaccine designed to mimic the N-Glycolyl-GM3 gangliosides. This monoclonal antibody is an Ab2-type-antibody which recognizes the Ab1 antibody called P3, the latter is a monoclonal antibody that specifically recognizes gangliosides as antigens. Since 1998 we initiated a clinical development program for these three compounds. Results of the phase I clinical trials proved that the three vaccines were safe and able to elicit specific antibody responses. In addition we were able to demonstrate the activation of the cellular arm of the immune response in patients treated with the GM3 vaccine. Although phase I trials are not designed to evaluate antitumor efficacy, it was encouraging to observe tumor shrinkage in some patients treated both with the GM3 and N-Glycolyl-GM3 vaccines. We have already begun a phase II program in several neoplastic diseases, with all three vaccines.

Asunto(s)

Antígenos de Neoplasias/inmunología , Vacunas contra el Cáncer/inmunología , Gangliósido G(M3)/análogos & derivados , Gangliósido G(M3)/inmunología , Alotipos de Inmunoglobulina Gm/inmunología , Animales , Ensayos Clínicos como Asunto , Humanos

RESUMEN

A total of 154 individuals belonging to three populations located at different altitude levels in northwest Argentina (San Salvador de Jujuy, 1,200 m; Tilcara, 2,500 m; Abra Pampa, 3,500 m) were studied for the GM, KM, HP, GC, PI and TF genetic systems. Individuals were selected on the basis of ethnocultural affiliation. Gene frequency values were found to be comparable to those reported for other South American populations. The populations studied showed a close genetic identity and an absence of interpopulation heterogeneity. Distribution of the GM phenotypes and haplotypes corresponds to historical data on human settlements in Jujuy Province. The presence of some alleles and the anthropological significance of the allele distribution are discussed, as are the effects of the admixture with Africans and Spaniards. The genetic pattern appears to be the result of a varying admixture due to the genetic isolation in populations located at various altitude levels.

Asunto(s)

Altitud , Frecuencia de los Genes , Marcadores Genéticos/fisiología , Alotipos de Inmunoglobulina Gm/genética , Indígenas Sudamericanos/genética , Adolescente , Adulto , Argentina , Femenino , Genética de Población , Haplotipos , Humanos , Alotipos de Inmunoglobulinas/genética , Masculino , Vigilancia de la Población , Población Rural , Muestreo

RESUMEN

A esquistossomose na forma hepatoesplênica associada a varizes sangrentas do esôfago, hiperesplenismo e/ou hipoevolutismo, em adolescentes, tem sido tratada clinicamente com oxamniquime e cirurgicamente por esplenectomia, ligadura da veia gástrica esquerda e auto-implante esplênico. Nos casos de recidiva hemorrágica, os pacientes são incluidos no protocolo de escleroterapia endoscópica das varizes esofageanas. No seguimento pós-operatório desses pacientes tem sido observado a manutenção de hiperglobulinemia G e M, e, eosinnofilia, fazendo supor a possibilidade de manutenção de carga parasitária residual ou reinfecção. vinte e quatro pacientes, entre 11 e 20 anos, foram submetidos a biópsia retal e oograma quantitativo, além do Kato-Katz para verificação dessa possibilidade. Em 17 pacientes, o oograma foi negativo, entretanto, em sete, o exame foi positivo, dos quais, quatro apresentavam ovos viáveis. O Kato-Katz, com ovos viáveis foi igualmente, positivo nesses quatros pacientes. Observou-se associação positiva entre os elevados níveis séricos de imunoglobulina G e a positividade do oograma. Os achados indicam uma carga parasitária residual ou reinfecção em cerca de 17 por cento dos pacientes, o que poderia estar interferindo na evolução clínica desses pacientes

Asunto(s)

Humanos , Masculino , Femenino , Adolescente , Oxamniquina/uso terapéutico , Recuento de Huevos de Parásitos , Esquistosomiasis mansoni/cirugía , Esplenectomía , Alotipos de Inmunoglobulina Gm

RESUMEN

BACKGROUND: The knowledge of the genic structure of a population is of great importance for evolutive studies. AIM: To estimate in a Chilean population sample from the low-middle and low socioeconomic strata of Santiago, haplotypes and allele frequencies for Gm and Km loci. SUBJECTS AND METHODS: The sample included 460 controls of a case-control study of typhoid fever. RESULTS: The G1m-G2m-G3m most frequent haplotypes were: za;..;g or 1,17;(-);21 = 0.4493;fn;b or 3;23;5,13 = 0.2522; f-,..;b or 3;(-);5,13 = 0.1389; zax;..;g or 1,2,17;(-);21 = 0.0685; za;..;b or 1,17;(-);5,13 = 0.0454; za;n;g or 1,17;23;21 = 0.0207; f;..;g or 3;(-);21 = 0.0129. The frequencies of Km alleles were 0.2391 and 0.7609 for Km1 and Km3 respectively. CONCLUSIONS: These frequencies are within those found in Amerindian and Caucasian populations as expected from the origin of the Chilean population. Gm haplotypes did not differ from Hardy-Weinberg equilibrium, while a significant lack of homozygous Km1/km1 was found in Km.

Asunto(s)

Alotipos de Inmunoglobulinas/genética , Alotipos de Inmunoglobulina Gm/genética , Fiebre Tifoidea/genética , Adolescente , Estudios de Casos y Controles , Niño , Preescolar , Chile , Femenino , Frecuencia de los Genes , Haplotipos , Humanos , Masculino , Fenotipo , Población Urbana

RESUMEN

The sample included 460 controls of a case control study of typhoid fever. The G1m-G2m-G3m most frequent haplotypes were: za,..;g or 1,17;(-);21=0.4493;fn;b or 3;23;5,13=0.2522;f-,..;b or 3;(-);5,13=0.1389; zax;..;g or 1,2,17;(-);21=0.0685;za;..;b or 1,17;(-);5,13=0.0454;za;n;g or 1,17;23;21=0.0207;f;..;g or 3;(-);21=0.0129. The frequencies of Km alleles were 0.2391 and 0.7609 for Km1 and km3 respectively. These frequencies are within those found in Amerindian and Caucasian populations as expected from the origin of the Chilean population. Gm haplotypes did not differ from Hardy-Weinberg equilibrium, while a significant lack of homozygous Km1/km1 was found in Km

Asunto(s)

Humanos , Masculino , Femenino , Adolescente , Fiebre Tifoidea/genética , Haplotipos/genética , Alotipos de Inmunoglobulina Gm/aislamiento & purificación , Cadenas kappa de Inmunoglobulina/genética , Estudios de Casos y Controles

Asunto(s)

Alotipos de Inmunoglobulina Gm/genética , Alotipos de Inmunoglobulinas/genética , Factor de Necrosis Tumoral alfa/genética , Lepra/genética , Lepra/inmunología , Interleucina-1/genética , Ligamiento Genético , Susceptibilidad a Enfermedades

RESUMEN

Gm and Km allotypes of immunoglobulins were determined in children with typhoid fever (Cases), in children without infectious diseases (Con-1), and in children with fever but no Salmonella in their blood or bone marrow (Con-2). Children were sampled from the urban population of Santiago; and they belonged to the low and low-middle socioeconomic strata. Cases had a higher frequency of [f;(-);b1,b3 or 3;(-);5,13] G1m, G2m, G3m haplotype than Con-1 and Con-2. Con-1 and Con-2 did not differ in their Gm haplotype or Km allele frequencies, but they differed in phenotype distribution. Con-1 deviated from Hardy-Weinberg equilibrium for Km due to a lack of Km 1-1 homozygotes. The relationship among these results, the ethnic origin of Chileans, and the differential susceptibility to typhoid fever are discussed.

Asunto(s)

Alotipos de Inmunoglobulinas/genética , Alotipos de Inmunoglobulina Gm/genética , Fiebre Tifoidea/patología , Adolescente , Análisis de Varianza , Estudios de Casos y Controles , Niño , Preescolar , Femenino , Frecuencia de los Genes/genética , Humanos , Alotipos de Inmunoglobulinas/sangre , Alotipos de Inmunoglobulina Gm/sangre , Alotipos de Inmunoglobulina Gm/clasificación , Masculino , Fenotipo , Fiebre Tifoidea/genética , Fiebre Tifoidea/microbiología

RESUMEN

Indigenous Indian groups comprise approximately 20% of Ecuador's population, the third largest percentage in all of Central or South America, yet immunogenetic data on these groups are lacking in the literature. In the course of population migration studies, sera collected from 65 Ecuadorians living in the northern province of Esmeraldas were typed for six GM and two KM markers. The study population consisted of 47 Cayapa Indians and 18 blacks of African origin, descendants of slaves imported into the area during the seventeenth century. The Cayapa demonstrated three GM phenotypes, two of which are common to other South American Indian tribes. The frequency of KM1 positive Cayapa Indians (63%) is similar to other South American Indian tribes, but is significantly greater than the Huaorani of eastern Ecuador (2%), the only other Ecuadorian Indian group for whom limited immunoglobulin allotype data are available (chi 2 = 35.8, P < 0.0001).

Asunto(s)

Alotipos de Inmunoglobulina Gm/genética , Alotipos Km de Inmunoglobulina/genética , Indígenas Sudamericanos/genética , Población Negra/genética , Ecuador , Pruebas de Inhibición de Hemaglutinación , Humanos , Fenotipo

RESUMEN

We have studied 506 Amerindians from three French Guiana groups: 194 Wayampi, living in Trois-Sauts, and 100 living in the Camopi area; 47 Emerillon also living in the Camopi area and 165 Wayana living on the Litani and Maroni rivers. All samples were tested for G1M (1,2,3,17), G3M (5,6,10,11,13,14,15,16,21,24,28) and KM(1) by the classical method of hemaglutination inhibition. The phenotype and haplotype distributions are presented and have been subjected to factorial analysis of correspondence. Two common GM haplotypes are GM1,17:21,28 and GM1,2,17;21,28 but with an important variation in frequency. A rare haplotype, GM1,17;21R,28, probably the result of a genetic anomaly, is frequent in the Emerillon (17%). These populations show no evidence of Negroid or Caucasian admixtures.

Asunto(s)

Frecuencia de los Genes , Alotipos de Inmunoglobulinas/genética , Indígenas Sudamericanos/genética , Guyana Francesa , Haplotipos , Pruebas de Inhibición de Hemaglutinación , Humanos , Alotipos de Inmunoglobulinas/sangre , Alotipos de Inmunoglobulina Gm/genética , Mutación , Fenotipo

RESUMEN

The fact that only a small percentage of excessive drinkers develop cirrhosis may be due to a genetic susceptibility to the disease. In order to identify possible genetic risk factors for cirrhosis, we studied mixed-race (Negroid-Caucasian) inhabitants of the French West Indies and compared: (1) the frequency of 51 HLA-A, -B, -C and -DR antigens in 41 subjects with alcoholic cirrhosis and in two control groups consisting of 41 excessive drinkers free of liver disease and 51 healthy non-drinkers; and (2) the frequency of Gm and Km haplotypes in the same groups. Analysis of the Gm system also determined the patients' ethnic origins. The frequency of the HLA-A2 antigen was significantly higher in the cirrhotic patients than in the control group of excessive drinkers (chi 2 = 4.47; P less than 0.05), while that of the HLA-B15 antigen was significantly lower (chi 2 = 5.14; P less than 0.05). The frequency of the Cw4 antigen was significantly higher in the cirrhotics than in the non-drinkers (chi 2 = 5.59; P less than 0.05). However, these differences did not persist when the number of comparisons was taken into account. The frequency of Gm and Km haplotypes was not significantly different in the three groups. In conclusion, complementary studies are required to determine the value of the Gm-Km system as a marker of susceptibility to alcoholic cirrhosis. Our results do not identify an association between HLA antigens and cirrhosis specific to a negroid ethnic group and support the notion that such an association is weak.

Asunto(s)

Población Negra/genética , Antígenos HLA/análisis , Alotipos de Inmunoglobulina Gm/análisis , Cadenas kappa de Inmunoglobulina/análisis , Cirrosis Hepática Alcohólica/inmunología , Población Blanca/genética , Adulto , Anciano , Biomarcadores/sangre , Susceptibilidad a Enfermedades , Femenino , Antígeno HLA-A2/análisis , Antígenos HLA-B/análisis , Antígeno HLA-B15 , Antígenos HLA-C/análisis , Humanos , Cirrosis Hepática Alcohólica/etnología , Masculino , Persona de Mediana Edad , Indias Occidentales

RESUMEN

This study examines the relationships between blood pressure, prevalence of hypertension, and the degree of black African admixture in the population of the Caribbean Island of La Désirade which is homogeneous with respect to the environmental factors and for which the socioeconomical stratification does not match racial origin. The degree of admixture was estimated by using both genealogical information and genetic markers. Blood pressure was repeatedly measured using an automatic sphygmomanometer. After adjustment for age, sex, ponderal index, Na/K urinary ratio, and clinical alcoholism, blood pressure and prevalence of hypertension were found to be significantly higher for the individuals having the largest proportion of genes of black origin. Identical results were obtained when either genetic markers or genealogical information were used as an individual--estimator of admixture.

Asunto(s)

Población Negra/genética , Presión Sanguínea , Hipertensión/epidemiología , Sistema del Grupo Sanguíneo ABO/genética , Adolescente , Adulto , Anciano , Antígenos de Grupos Sanguíneos/genética , Femenino , Frecuencia de los Genes , Antígenos HLA/genética , Hemoglobinas/genética , Humanos , Alotipos de Inmunoglobulina Gm/genética , Antígenos del Grupo Sanguíneo de Lewis/genética , Masculino , Persona de Mediana Edad , Sistema del Grupo Sanguíneo Rh-Hr/genética , Indias Occidentales , Población Blanca/genética

RESUMEN

This study examines the relationships between blood pressure, prevalence of hypertension, and the degree of black African admixture in the population of the Caribbean Island of La Desirade which is homogenous with respect to the environmental factors and for which the socioeconomical stratification does not match racial origin. The degree of admixture was estimated by using both genealogical information and genetic markers. Blood pressure was repeatedly measured using an automatic sphygmomanometer. After adjustment for age, sex, ponderal index, Na/K urinary ratio, and clinical alcoholism, blood pressure and prevalence of hypertension were found to be significantly higher for the individuals having the largest proportion of genes of black origin. Identical results were obtained when either genetic markers or genealogical information were used as an individual-estimator of admixture. (AU)

Asunto(s)

Humanos , Adolescente , Adulto , Persona de Mediana Edad , Anciano , Masculino , Femenino , Presión Arterial , Hipertensión/epidemiología , /genética , Sistema del Grupo Sanguíneo ABO/genética , Antígenos de Grupos Sanguíneos/genética , /genética , Frecuencia de los Genes , Hemoglobinas/genética , Antígenos HLA/genética , Alotipos de Inmunoglobulina Gm/genética , Antígenos del Grupo Sanguíneo de Lewis/genética , Sistema del Grupo Sanguíneo Rh-Hr/genética , Indias Occidentales

RESUMEN

Our recent segregation analysis, carried out on 27 large pedigrees from a Caribbean island (Desirade), has shown the presence of recessive major gene(s) controlling susceptibility to leprosy per se and nonlepromatous leprosy, respectively. Linkage analysis was performed between each of these two detected genes and each of five markers typed in the Desirade population: HLA, ABO, Rhesus, Gm and Km. No positive significant lod score was observed. However, for leprosy per se close linkage was excluded with Rhesus and Gm (and also with ABO and HLA, considering a lower value for the frequency of the gene controlling susceptibility to leprosy per se). The highest lod score, although not significant, was obtained between the gene for nonlepromatous leprosy and ABO. Our overall results, joined with previous studies and experimental data, suggest that the gene controlling susceptibility to leprosy per se and that controlling susceptibility to nonlepromatous leprosy might be different, acting at successive stages of the immune response to infection with Mycobacterium leprae.

Asunto(s)

Ligamiento Genético , Marcadores Genéticos , Lepra Lepromatosa/genética , Lepra/genética , Sistema del Grupo Sanguíneo ABO/genética , Susceptibilidad a Enfermedades , Antígenos HLA/genética , Humanos , Alotipos de Inmunoglobulinas/genética , Alotipos de Inmunoglobulina Gm/genética , Sistema del Grupo Sanguíneo Rh-Hr/genética , Indias Occidentales