The distribution of the human liver alcohol dehydrogenase, ADH2, and aldehyde dehydrogenase, ALDH2, genotypes in 21 different populations comprising Mongoloids, Caucasoids, and Negroids was determined by hybridization of the amplified genomic DNA with allele-specific oligonucleotide probes. Whereas the frequency of the ADH1(2) allele was found to be relatively high in the Caucasoids, Mexican Mestizos, Brazilian Indios, Swedish Lapps, Papua New Guineans and Negroids, the frequency of the ADH2(2) gene was considerably higher in the Mongoloids and Australian Aborigines. The atypical ALDH2 gene (ALDH2(2)) was found to be extremely rare in Caucasoids, Negroids, Papua New Guineans, Australian Aborigines and Aurocanians (South Chile). In contrast, this mutant gene was found to be widely prevalent among the Mongoloids. Individuals possessing the abnormal ALDH2 gene show alcohol-related sensitivity responses (e.g. facial flushing), have the tendency not to be habitual drinkers, and apparently suffer less from alcoholism and alcohol-related liver disease.

It has been suggested that the higher susceptibility of Hispanics to metabolic disease is related to their Native American heritage. A frequent cholesterol transporter ABCA1 (ATP-binding cassette transporter A1) gene variant (R230C, rs9282541) apparently exclusive to Native American individuals was associated with low high-density lipoprotein cholesterol (HDL-C) levels, obesity and type 2 diabetes in Mexican Mestizos. We performed a more extensive analysis of this variant in 4405 Native Americans and 863 individuals from other ethnic groups to investigate genetic evidence of positive selection, to assess its functional effect in vitro and to explore associations with HDL-C levels and other metabolic traits. The C230 allele was found in 29 of 36 Native American groups, but not in European, Asian or African individuals. C230 was observed on a single haplotype, and C230-bearing chromosomes showed longer relative haplotype extension compared with other haplotypes in the Americas. Additionally, single-nucleotide polymorphism data from the Human Genome Diversity Panel Native American populations were enriched in significant integrated haplotype score values in the region upstream of the ABCA1 gene. Cells expressing the C230 allele showed a 27% cholesterol efflux reduction (P< 0.001), confirming this variant has a functional effect in vitro. Moreover, the C230 allele was associated with lower HDL-C levels (P = 1.77 x 10(-11)) and with higher body mass index (P = 0.0001) in the combined analysis of Native American populations. This is the first report of a common functional variant exclusive to Native American and descent populations, which is a major determinant of HDL-C levels and may have contributed to the adaptive evolution of Native American populations.

Five hundred and ten students of the Universidad Nacional Autónoma de México were tested to determine the distribution of ABO, MN, Rr-Hr blood groups, and serum haptoglobin, albumin, and Factor Bf types. Based on the results we found that the proportion of Indian and White genes are of 56.16 and 43.84%, respectively in the dihybrid model and 2.93, 56.22, and 40.85% for Blacks, Indians, and Whites in the trihybrid one. The present study reveals a higher proportion of Indian genes in the Mexico City population than estimated in previous publications. Reasons why the present results apply to a much larger group of Mexico City mestizos than the previous ones are given.

Three hundred ninety-three individuals from the Universidad Autónoma de Puebla and its University Hospital were studied to determine the distribution of ABO, MN, Rh-Hr, Duffy, and Diego blood groups; red cell hemoglobin and glucose-6-phosphate dehydrogenase variants; and serum haptoglobins, albumins, and factor Bf types. With the results we estimated that the proportions of black, indian, and white genes are 10.7%, 56.3%, and 33.0%, respectively, in a trihybrid model. Reasons are given as to why the black ancestry may be artifically high, and it is pointed out that independent confirmation with other markers is needed before the figure can be accepted as a true value.

Seven genetic systems were used to investigate the racial composition of a sample from a low-income Mexico City Mestizo group, finding estimates of 0.590, 0.348, and 0.062 of Indian, White, and Black ancestry, respectively. The results are similar to another Mexico City group studied previously and to several Mestizo populations from different parts of the country. The one thing in common in all these groups is low socioeconomic status. There is only one report suggesting that Mexico City Mestizos have around 70% White ancestry, and there is reason to believe the sample was taken from a high socioeconomic group. It is suggested that low socioeconomic Mexican Mestizo groups are characterized by a high Indian ancestry, above 50%. © 1995 Wiley-Liss, Inc.