HLA polymorphism and evaluation of European, African, and Amerindian contribution to the white and mulatto populations from Parana, Brazil

Human Biology, Aug 2000 by Probst, C M, Bompeixe, E P, Pereira, N F, de O Dalalio, M M, Et al

Abstract Polymorphism of classical HLA-A, HLA-B, HLA-C, HLA-- DR, and HLA-DQ genes differs greatly among populations, both in frequencies and in the presence of alleles and haplotypes particular to population groups, making these genes powerful tools for the study of origins of populations and their degree of admixture. Antigen, allele, and haplotype frequencies, together with linkage disequilibrium patterns, are reported for 2 populations in the southern Brazilian state of Parana, one of predominantly European ancestry (white), the other of predominantly African and European ancestry (mulatto). Genetic distance estimates between the 2 groups and other populations studied previously, and of degree of admixture, were performed. In accordance with phenotypic classification, the white population is of predominantly European origin (80.6%), with a smaller contribution of African (12.5%) and Amerindian (7.0%) genes. The mulatto population consists of African (49.5%) and European (41.8%) ancestry, with a smaller but significant contribution of Amerindian (8.7%) ancestry. On the basis of history and population genetics, there is controversy regarding the Amerindian contribution to Parana's gene pool. These results provide a better picture of Parana's ethnic constitution and on the Amerindian contribution to the white and mulatto populations.

KEY WORDS: HLA POLYMORPHISM, ADMIXTURE, BRAZIL, LINKAGE DISEQUILIBRIUM

The HLA system comprises a set of genes located in the human Major Histocompatibility Complex (MHC), which contains over 120 genes predicted to be expressed. Although many are still of unknown function, it has been estimated that about 40% of the expressed genes have immune system function (The MHC Sequencing Consortium 1999). HLA molecules play a cardinal role in immune responses, in that T lymphocytes recognize antigens only when bound to HLA molecules, and natural killer (NK) cell function depends on HLA class I molecule expression (Karre et al. 1986).

Besides function, other properties of the HLA system and typing applications attract great interest. One of them is histocompatibility, since HLA compatibility between graft donor and recipient is important to a good outcome of transplantation. Further, HLA genes have a high degree of polymorphism, and linkage disequilibrium between alleles of the closely linked loci is common. The different patterns of HLA allele frequency distribution make it possible to distinguish human populations. Identifying haplotypes of specific populations is important because populations differ on this basis, and HLA haplotypes are often better markers for population genetics than alleles. In addition, identifying linkage disequilibrium patterns in several human populations supplies valuable data for understanding the mechanisms of origin and maintenance of linkage disequilibrium itself (Sotomaior et al. 1998).

Since HLA antigen frequency depends on the ethnic composition of the population analyzed, a brief report on the colonization of the state of Parana and therefore its ethnic background is given below.

Parana is located in the southern region of Brazil (Figure 1), between 22(deg)29'30"-26(deg)42'59"S and 48(deg)02'24"-54(deg)37'38"W. Its economy is based mainly on agriculture, but the commercial and industrial sectors are also considerably developed. It has about 8.96 million inhabitants, according to the 1996 Census, with nearly 16% living in the capital, Curitiba.

The region that encompasses the state of Parana had been populated by indigenous people for approximately 10,000 years before the arrival of European colonizers (Prous 1991). The first Iberian visitors encountered Amerindians belonging to several different tribes, mostly of the Tupi-Guarani group.

Most of Parana was included in the theoretical Spanish territory that resulted from the Tordesilhas Treaty in 1494, a revision of Pope Alexander VI's 1493 partition of the New World between Spain and Portugal. Parana was joined to Brazil during the second half of the 18th century. Except for a brief and unsuccessful attempt by Spaniards at colonization in the middle of the 16th century, there was no European presence in the region until the 17th century, when Portugal began to colonize the coastal area of Parana (Martins 1940; Michaele 1969). Because of the area's economic weakness, immigration proceeded very slowly during the 18th century, when settlers came to occupy the 'first prairie' region (Figure 1). A boost in the number of settlers occurred around 1750, as a result of a commercial route on the 'second prairie' (Figure 1). At that time, the population of eastern Parana was of Portuguese, Amerindian, and Spanish origin, with Spaniards being minor contributors. African-Brazilians, predominantly Bantu-speakers from Angola and Mozambique (Martins 1940; Michaele 1969; Zago et al. 1992) were also present, but in fewer numbers than in other Brazilian regions, because of the weaker economy in comparison to northeastern and eastern Brazil. The Amerindians belonged mainly to the Guarani and Kaingang tribes, the major Amerindian tribes of southern Brazil (Michaele 1969; Petzl-Erler et al. 1993), although smaller groups, such as the Xokleng and Xeta, were also present (Mota 1994).