LA DIABETES MELLITUS (DM) comprende un grupo heterogéneo de desordenes hiperglucémicos clasificados en subgrupos de acuerdo a su fisiopatología y etiología, entre los cuales se destacan la Diabetes Mellitus tipo1 (DM1) y la diabetes mellitus tipo 2 (DM2). La DM1 es de aparición temprana y una absoluta escasez de insulina hace que los pacientes sean insulino dependientes desde el inicio de los síntomas y la (DM2), de inicio en la edad adulta y no todos los pacientes que la sufren son insulino dependientes. La DM1 se clasifica como DM1A si es el efecto de una respuesta autoinmune por parte de las células del páncreas y DM1B si la causa es desconocida (idiopática). Los estudios sobre la etiología de DM1 han demostrado que ambos subtipos tienen un fuerte componente genético, pero el patrón de herencia es complejo, ya que su patogénesis puede ser el resultado de la interacción de variantes en múltiples genes con factores medioambientales. Los estudios genéticos sobre DM1 han permitido identificar loci de suceptibilidad que se denominan IDDM, así para DM1A se encontró el primer locus (IDDM1) en la región HLA-DR/DQ, situada en 6p21, que modula el efecto de otros genes implicados en la enfermedad, el segundo (IDDM2) se localiza en 11p15 donde se encuentra el gen de la Insulina. Es decir, DM1 presenta gran heterogeneidad genética, de tal manera, que se han identificado más de 18 loci implicados en susceptibilidad a ella, entre ellos 3 en el cromosoma 2 (IDDM 7,12 y 13) y uno en el cromosoma 14 (IDDM11), este último asociado a DM1B. El objetivo de este estudio consistió en la búsqueda de loci en los cromosomas 2 y 11 involucrados en la susceptibilidad a DM, en 3 familias antioqueñas, para lo cual se realizó análisis de ligamiento paramétrico a 23 marcadores microsatélites en el cromosoma 2 y a 18 en el cromosoma 11. A las familias, codificadas como DM1(11afectados), familia 1 (2 afectados) y familia10 (3 afectados), se les realizó simulación para determinar el poder para hacer análisis de ligamiento y los resultados mostraron que presentaban suficiente poder para realizarlo, puesto que en DM1 la razón de disparidad máxima (Lod score o Z máximo) fue de 3.57, sin recombinación (θ=0), el cual es superior a 3, el valor aceptado para determinar ligamiento, y al tomar las tres familias en conjunto se obtuvo un Z máximo de 5.76. Con el análisis de ligamiento para el cromosoma 11, se halló que solo en la familia 10 se presentaba un valor positivo de Z; 1.18 al marcador D11S925 con ?=0, muy superior al de la simulación de esta familia (0.75), con respecto al cromosoma 2, se obtuvieron valores de Z positivos al marcador D2S319 en DM1 y familia 10, 2.08 y 0.88 respectivamente, con θ=0. Al tomar las tres familias como un todo y calcular Z para los marcadores D11S925 y D2S319, se obtuvo un valor de 2.5, con θ=0, lo cual está corroborando que en las familias analizadas están involucrados 2 loci, situados en las regiones de los cromosomas 11 y 2 señaladas por dichos marcadores. Si se tiene en cuenta que el marcador D11S925 está situado en la región 11q23-3 y el D2S319 en la 2qter, se puede decir, que con este trabajo se han identificado 2 loci nuevos de susceptibilidad a DM1 en la población antioqueña, ya que estas regiones no concuerdan con las reportadas hasta el presente; además, como se hizo análisis de ligamiento a IDDM1, con resultados negativos (datos no mostrados), la DM1 estudiada podría clasificarse como DM1B.

DIABETES MELLITUS (DM) comprises e heterogeneous group of hypoglycemic disorders, that are grouped according to their physiopathology and etiology; the most notorious ones are type 1 DM (DM1) and type 2 DM (DM2); DM1 is characterized by early onset and absolute lack of insulin; therefore, patients suffering from it depend on insulin since the beginning of their symptoms; in contrast, DM2 manifests during adult life and not all patients depend on insulin. DM1 is classified as DM1A when it results from an autoimmune response of pancreatic b cells, and DM1B if it is of unknown origin (idiopathic). Studies on the etiology of DM1 have revealed that both types have a strong genetic component but their inheritance pattern is complex since its pathogenesis may result from the interaction with environmental factors of variants in multiple genes. By means of genetic studies on DM1, susceptibility loci known as IDDM have been identified, namely: for DM1A the first locus (IDDM1) was found in the HLA-DR/QD region, located in 6p21, that modulates the effect of other genes involved in the disease; the second one (IDDM2) is located in 11p15, the site of the insulin gene. That means, DM1 exhibits wide genetic heterogeneity so that more than 18 loci involved in susceptibility to this disease have been identified, among them, 3 on chromosome 2 (IDDM 7, 12, and 13), and 1on chromosome 14 (IDDM11), the latter being associated to DM1B. The aim of this study was the search for loci on chromosomes 2 and 11 involved in the susceptibility to DM, in three families from Antioquia, Colombia; for that purpose, parametric linkage analysis was performed to 23 microsatellite markers on chromosome 2, and to 18 on chromosome 11. In order to determine the power for making linkage analysis, simulation was carried out on the families, coded as DM1 (11 affected members), family 1 (2 affected members), and family 10 (3 affected members); results demonstrated power enough for that purpose since in DM1 the maximum odds ratio (Lod score or Z maximum) was 3.57 without recombination (=0=0), above 3, the accepted value for determining linkage; when the three families were taken together, a maximum Z of 5.76 was obtained. With the linkage analysis for chromosome 11, it was found that only in family 10 there was a positive Z value, 1.18 to marker D11S925 with =0=0, above the simulation value for this family (0.75); as regards chromosome 2, positive Z values were obtained to marker D2S319 in DM1 and family 10: 2.08 and 0.88, respectively, with =0=0. When the three families were taken as a whole and Z values were calculated for markers D11S925 and D2S319, a value of 2.5 was obtained, with =0=0, which confirms that in the analysed families 2 loci are involved, located in the regions of chromosomes 11 and 2 signaled by such markers. If it is taken into account that the D1S925 marker is located in the region 11q23-3, and the D2S319 marker, in the region 2qter, it may be said that in this work two new loci of susceptibility to DM1 have been identified in three families from Antioquia, Colombia, since these regions do not agree with those so far reported; besides, since results were negative in linkage analysis to IDDM1(data not shown), the studied cases of DM1 could be classified as DM1B.

The possible relationship between erythrocyte antigens and the presence of malaria infection by P. vivax and P. falciparurn was sought in four different ethnic groups of two departments of Colombia. Malaria infection by P. falciparum was found in 91.4% of malaria infected blacks. No significant differences were found between the presence of malaria infection and ABO antigens. In the other blood groups, it was observed that groups MNSs conferred black people a greater Rr for malaria by both species of Plasmodium and that Duffy-negative blacks and indians appeared to be resistant to P. vivax infection. A predominance of P. vivax infection was observed in Katio indians while P.falciparum was predominant in Kuna indians; the reason for this finding still needs to be explored.

Con el presente estudio se evalúa la relación existente entre la infección por P. vivax y P. falciparum y los antígenos eritrocitos de cuatro diferentes grupos étnicos en Colombia. P. falciparum se encontró causando malaria en el 91.4% de los individuos de raza negra que tuvieron malaria. No hubo diferenciais significativas entre la infección malaria y los antígenos ABO. La presencia de grupos del sistema MNSs en persona de raza negra confiere un mayor riesgo relativo por la infección para las dos especies de Plasmodium, igualmente hay mayor riesgo cuando se pertenece a la raza negra o indígena y el grupo Duffy es negativo. La infección por P. vivax predomina en los indios Katios pero en los Kunas prevalece P. falciparum.

Foram estudados os antigenos HLA e a relação destes com a infecção malárica em 4 diferentes grupos étnicos da Colômbia (América do Sul); dois grupos de índios (Kunas e Katios), um grupo de negros e um grupo que apresentava ancestrais mistos. Foram estudadas 965 pessoas, das quais 415 com malária e 550 como controles. A freqüência dos antígenos HLA-A, B e C foram determinados nos quatro grupos estudados. A associação de cada antígeno HLA com a infecção por P. vivax e P. falciparum foi avaliada. Os antígenos HLA 6-9 encontrados no grupo de ancestrais mistos, de um modo geral não foram observados nos grupos de negros e índios (Kunas e Katios). Nos grupos étnicos mencionados, os antigenos B5, B13, B15, Cw2 e Cw4 apresentaram uma associação limítrofe com a infecção por malária. Entretanto, no grupo étnico de ancestrais mistos foi observada uma associação estatisticamente significativa com a infecção malárica, sendo que a presença de A9, Aw19, B17, B35 e Z98 (B21-B45: determinantes de reação cruzada) mostrou poucas diferenças quando as infecções por P. vivax e P. falciparum foram consideradas individualmente. Esse achado pode representar, de um modo geral, uma falta de resistência a malária no grupo portador de antigenos de origem caucasiana, os quais tem tido um contacto direto e permanente com a malária somente nos últimos 65 anos. Em contraste, os índios (Kunas e Katios) e os negros tem vivido durante séculos em áreas endêmicas para malária, é possível que um sistema de seleção natural tenha sido desenvolvido permitindo que somente aqueles indivíduos capazes de iniciar uma resposta imune à malária sobrevivam.

HLA antigens and their relationship with malaria infection were studied in four different ethnic groups in Colombia (South America): two groups of indians (Kunas and Katios), one of negroes and a group of mixed ancestry. A total of 965 persons were studied, 415 with malaria and 550 as controls. HLA-A,B, and C antigen frequencies in the four groups are reported. The association of each HLA antigen with malaria infection due to P. vivax and to P. falciparum was evaluated. Negroes, Kunas and Katios indians variously lack from 6 to 9 of the HLA antigens found in the mixed group. In the designated ethnic groups, antigens B5, B13, B15, Cw2 and Cw4 showed borderline association with malaria infection. However, in the mixed ethnic group, statistically significant associations were found with malaria infection and the presence of A9, Aw19, B17, B35, and Z98 (a B21-B45: crossreacting determinant) with few differences when P. vivax infection and P. falciparum infection were considered individually. This finding may represent a lack of general resistance to malaria in the group that harbors antigens of Caucasian origin. These individuals have been in direct and permanent contact with malaria only in the past 65 years. In contrast, indians, both Kunas and Katios, and Negroes have lived for centuries in malaria endemic areas, and it is possible that a natural selection system has developed through which only those individuals able to initiate an acute immune response to malaria have survived.