Distribution of Albumin Variants in Indians and Non-Indians of Mexico RUBEN LISKER, LESVIA COBO A N D GUILLERMINA MORA Departamento de Geneticu, Instituto Nacioncil de In Nutricion, Saiz Fernando SIN, Mexico 22, D.F . ABSTRACT The distribution of albumin variants amongst several Mexican Indian and non-Indian (Mestizo) groups was studied. Of the former, a total of 1606 individuals belonging to 1 1 different tribes were examined with a n overall frequency of 1 . 5 % of Albumin Mexico fairly uniformly distributed in all four main linguistic groups. The 2548 Mestizos studied belong in six groups, two from Mexico City and four from elsewhere i n the country. The first of the Mexico City groups consisted of 1313 individuals randomly chosen from the outpatient clinic of the Instituto Nacional de la Nutricion, while the rest included healthy individuals. The overall frequency was 1.9%, also fairly evenly distributed, with no difference between the hospital population and the others. No anomalous albumin, other than Albumin Mexico was encountered i n the whole study. It is concluded that the similarity between Indians and Mestizos is due to the high Indian component of the latter and that the presence of albumin Mexico is a good anthropological marker for this region of the world. Since Scheurlen's description in 1955 of a patient with two serum albumin bands demonstrated by paper electrophoresis, many more variants have been described. With the use of starch gel electrophoresis at least 12 different types can be distinguished (Weitkamp et al., '67; Weitkamp, Franglen et al, 69; Weitkamp, Basu, Gall and Brown, '69; Arends et al., '69; Lau et al., '69); the study of their dye-binding properties can apparently further differentiate samples with similar or identical electrophoretic mobilities (Tarnoky et al., '70). Their clinical significance is not clear; some investigators have found high cholesterol levels associated with albumin variants (Earle et al., '59; and Tarnoky and Lestas, '64); others have reported a high frequency of bone and joint complaints among several members of a family with a slow moving variant (Laurel1 and Nilehn, '66); while Melartin et a1 ('68) could find no clinical or laboratory abnormalities i n North American Indians homozygous or heterozygous for Albumin Naskapi. Most of the reported serum albumin types have been encountered in one or at best a few isolated families; notable exceptions are the Naskapi and Mexico variants which are found in appreciable frequencies in different communities AM. J. PHYS. ANTHROP.. 35: 113-124. (Melartin and Blumberg, '66; Melartin et al., '68; Lisker and Zarate, '68). The Naskapi variant seems to be confined to Amerindians inhabiting the Northern part of the American Continent while Albumin Mexico has been described in Indians living in Southern United States and i n Mexico (Melartin et al., '67). In South America, two variants have been described, Albumin Maku in Brazil (Weitkamp and Chagnon, '68) and Albumin Warao in Venezuela (Arends et al., '69); each has been found in only one Indian tribe and, apparently, with a low frequency. The main purpose of the present study is to investigate . t h e distribution of albumin variants i n various Mexican Indian and Mestizo groups, to further characterize these populations that have been studied rather extensively i n the past. I n addition, some information was obtained to learn whether individuals with albumin variants are more prevalent in hospital groups than in the general population. MATERIAL AND METHODS A total of 1606 samples of individuals belonging to 11 Mexican Indian groups 1 This work was supported by grant HD 00862 from the U.S.P.H.S. 119 120 R. LISKER, L. COB0 AND G. MORA were obtained (table 1). They include several representatives of each major linguistic group: the Nahua, Otomi and Cora belong to the Macro-Nahua; the Huasteco, Tzeltal-Tzotzil and Chol to the Macro-Maya; the Zapoteco, Mixteco, Mazateco and Mixe to the Macro-Mixteco, and the Tarasco to the Tarasco. The habitats and geographic location of these groups is varied (fig. 1); some of the Nahua and the Huasteco inhabit the East Coast while the rest live in mountaneous areas near Mexico City or in the state of Oaxaca. Their population size is extremely varied; the Nahua number approximately 700,000 individuals, while no more than 3,000 persons form the Cora group. A complete general description of these tribes has been made in previous publications (Rodriguez et al., '63; Cordova et al., '67). With the exception of the Huasteco, all the populations were studied i n schools for Indian boys, where they spend three years learning Spanish and crafts. Most individuals were not related and often came from different villages. The Nahua samples were obtained in four schools, two located i n the State of Puebla, one i n Hidalgo and one i n Veracruz; the habitats are quite different but as no difference i n the distribution of albumin was encountered the individuals were pooled. The Huasteco samples were obtained in two villages located in the States of Veracruz and Tamaulipas; most individuals were adults and half of them women, while in the schools only boys were investigated and their ages ranged from 10 to 16 years. Several Mestizo groups were studied. The largest was formed by 1313 individuals attending the outpatient department of our Institution. They were sampled without our knowledge of their diagnosis. Most persons belonged to a low socio-economic class and both sexes were fairly equally represented. The second largest Mestizo group was formed by 661 pregnant females of low-middle socioeconomic class attending a large maternity hospital. The 257 mestizo individuals of the states of Tlaxcala and Hidalgo were sampled i n connection with a n investiga- INDIANS @ NAHUA @ OTOMl @ CORA @ HUASTECO 0 TZELTAL-TZOTZIL MESTIZOS @ MEXICO @ VERACRUZ @ @ CAMPECHE WEST COAST @ ZAPOTECO Fig. 1 CITY @ TLAXCALA-HIDALGO Geographic location of the Indian a n d Mestizo groups included in this study. 121 ALBUMIN VARIANTS IN MEXICO tion of the frequency and etiology of anemia in our rural population; most individuals were non-related adult male farmers. The samples of the last three groups were taken in a project to investigate several genetic hematologic traits in the Mexican population, and the results, including the population characteristics, have been published (Lisker, et al., '65; Lisker, et al., '69). They are non-related males of a tri-hybrid group having IndianWhite-Negro intermixture. From every individual 5 ml of blood was collected by venous puncture in glass tubes without anticoagulant. The samples were kept cold and shipped to Mexico City where they arrived within 48 hours of collection. The sera were separated and kept frozen until time of study. The majority of the samples were tested within one month of collection. Those from the Cora, Chol and Mazateco Indians, and the West Coast hybrid groups had a storage period of approximately one year. This is important as under our storage conditions albumin denatures after a year and artifacts may appear (Lisker, '70) which prevent accurate determinations. The screening procedure employed was a horizontal starch gel electrophoresis system using Ashton and Braden's discontinous buffer at pH 8.6 (Melartin, et al., '67). The gels were prepared with hy- drolyzed starch (Connaught) at a concentration 25% greater than that recommended by the supplier. All abnormal samples were restudied simultaneously using three systems: (1) the above described one; (2) another horizontal starch gel with a buffer recommended by Weitkamp, Franglen et. al., ('69), containing in the tray 0.03 M tris (hydroxymethil) aminomethane, 0.0043 M EDTA and 0.27 M boric acid (pH 6.4), and with the gel buffer of a 1: 6.2 dilution of the above; and (3) a vertical acrylamide gel with a tris-glycine buffer pH 9.2. In the latter the serum was diluted 1:5 while in the starch gel systems it was used undiluted. RESULTS AND DISCUSSION Tables 1 and 2 show the results seen in the Indian and non-Indian groups, respectively. In both groups the same anomalous variant, Albumin Mexico, was the only abnormality present, always in the heterozygous state, and no differences between them could be demonstrated in any of the three electrophoretic systems employed. We realize that this is not proof of identity and it might be that more than one albumin type could be present, but until proven otherwise, it will be assumed that all are indeed Albumin Mexico. Using the nomenclature of Weit- TABLE I Distribution of nlbumin variants in 1 1 Mexican Indiun groups Main linguistic group Subgroup Nahua Macro-Nahua * Location (State of the Republic) No. studied 440 Puebla, Hidalgo, Veracruz Hidalgo Nayarit 6 1.36 5 2 5.00 2.41 4 0 0 2.13 0.00 0.00 3 1.18 0.00 Otomi Cora 1 100 Macro-Maya Huasteco Tzeltal-Tzotzil Chol 1 188 144 138 Veracruz, Tamaulipas Chiapas Chiapas Macro-Mixteco Zapoteco 1 Mixteco Mazateco 1 Mixe 255 48 22 21 Oaxaca Oaxaca Oaxaca Oaxaca Tarasco 167 Michoacan Tarasco 83 Total: 1606 Albumin Phenotype Mexico Heterozygous No. lo 0 0 0 0.00 0.00 5 2.99 25 1.56 These results have been partially reported (Lisker, '70). The Nahua were sampled in four communities and the Zapoteco i n two. 1 122 ALBUMIN VARIANTS IN MEXICO TABLE 2 Distribution of a l b u m i n v a r i a n t s i n 2548 M e s t i z o i n d i v i d u a l s w i t h dgfeerent h a b i t a t s Location No. studied Albumin Phenotype Mexico Heterozygous % No. Mexico City Mexico City TlaxcalaHidalgo 3 Veracruz 4 Campeche 4 West Coast 4 1313 661 27 8 2.06 1.21 257 109 109 99 12 1 0 1 4.67 0.92 Total: 2548 49 1.92 0.00 1.01 1 Samples obtained a t random i n the outpatient clinic of our Institution. 2 Normal pregnant females sampled at random in a large maternity hospital. 3 Adult male farmers. Previously (Lisker . reported . and Zarate, '68). 4 Adult male tri-hybrid Mestizos with Indian-NegroWhite intermixture. Previously reported (Lisker and Zarate, '68). day frequency, and the more general one of why albumin variants are common in the American Indian and not in other populations, are difficult to answer. They may have enjoyed at some time in history a selective advantage, but the mechanism of this is obscure and the physiological studies comparing the different types of albumins have so far not been very informative in this respect (Blumberg, '69). It should be pointed out that the prevalence of Albumin Mexico in the Hospital population investigated (see table 2), seems to be very similar to that of the other Mestizo groups examined. The sample size is too small to permit any conclusions, but at least there is no evidence that the possession of Albumin Mexico makes an individual more prone to develop disease. In addition, the distribution of the main diagnosis of the 27 individuals of the Hospital group who had Albumin Mexico, is grossly what would be expected in our Institution, there being no indication that albumin types are unevenly distributed among diseases. kamp, Franglen et al., ('69), based on the relative electrophoretic mobility of albumins in four different buffer systems, i t corresponds to the 3,3,2,3, variety. In this nomenclature, every number refers to the relative electrophoretic mobility of the ACKNOWLEDGMENTS sample in one of the buffer systems. The slowest moving gets number 1, while The authors wish to acknowledge the number 8 is assigned to the fastest. unlimited help given by the authorities, The distribution among the four main linguistic Indian groups is fairly uniform personnel and pupils of all the schools and the differences not significant; x 2 for Indian boys studied. 3 d.f. =6.18, ~ 2 0 . 1 0 .The differences LITERATURE CITED within the Mestizos are significant; ~2 5 d.f. = 15.64, pSO.01. However, most Arends, T., M. L. Gallango, M. Layrisse, J. Wilbert and H. 0. Heinen 1969 Albumin Warao: of the 'X value is due to the very high New type of human alloalbuminemia. Blood, prevalence found in the Tlaxcala-Hidalgo 33: 414-420. group, which may be just a sampling Blumberg, B. S. 1969 The epidemiology of alloalbuminemia. Arch. Envir. Health., 1 8 : 1-3. phenomenon as the number studied is M. S., R. Lisker and A. Loria 1967 relatively low. The overall prevalence of Cbrdova, Studies on several genetic hematological traits Albumin Mexico in the Indian group is of the Mexican population. XII. Distribution of very similar to that in the mestizo ( ~ 2 blood group antigens i n twelve Indian tribes. Am. J. Phys. Anthrop., 26: 55-65. 1 d.f. = 0.74, p20.30), which is probably D . P., M. P. Hutt, K. Schmid and D. Gitlin explained by the fact that the Indian Earle, 1959 Observations on double albumin: a gecomponent in the Mestizo is relatively netically transmitted serum protein anomaly. large. J. Clin. Invest., 38: 1412-1420. We have no information of the distri- Lau, T., F. W. Sunderman, S. S. Agarwal, A. I. Sutnick and B. S. Blumberg 1969 Genetics of bution of Albumin Mexico in Central albumin Gainesville, a new variant of human America; however i t seems clear that this serum albumin. Nature, 221: 66-68. variant is fairly frequent in Mexico and Laurell, C. B., and J. E. Nilkhn 1966 A new type of inherited serum albumin anomaly. J. its presence is probably a good anthroClin. Invest., 45: 1935-1945. pological marker of Amerindian and Lisker, R., A. Loria and M. S. Cordova 1965 Mestizos in this part of the world. The Studies on several genetic hematological traits question as to why it attained its present of the Mexican population. VIII. Hemoglobin R. LISKER, L. COB0 AND G. MORA S, Glucose-6-Phosphate Dehydrogenase deficiency, and other characteristics in a malarial region. Am. J. Hum. Genet., 17: 179-187. Lisker, R., and G. Zkrate 1968 Distribution de la Albumina Mexico en Mexico. Rev. Invest. Clin. (Mex.), 20: 421-427. Lisker, R., M. S. Cordova and G. Zarate 1969 Studies on several genetic hematological traits of the Mexican population. XVI. Hemoglobin S and Glucose-6-Phosphate Dehydrogenase deficiency i n the East Coast. Am. J. Phys. Anthrop., 30: 349-354. 1970 Genetic polymorphisms in Lisker, R. 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