Absence of the E2 allele of apolipoprotein in Amerindians

Guilherme B. Marin1, Marli H. Tavella1, João F. Guerreiro2,Sidney E.B. Santos2
and Marco A. Zago1
1 Departamento de Clínica Médica, Faculdade de Medicina de Ribeirão Preto, Universidade de São Paulo, 14049-900 Ribeirão Preto, SP, Brasil. Tel.: (016) 633-8071, Fax: (016) 633-4009. E-mail: marazago@usp.br. Send correspondence to M.A.Z.
2 Laboratório de Genética Humana e Médica, Universidade Federal do Pará, 66075-900 Belém, PA, Brasil.

Determination of the ApoE allele distribution in five South American Amerindian tribes revealed absence of the ApoE2 allele, accompanied by high ApoE3 and low ApoE4 allele frequencies for most tribes, a distribution only previously reported for the Inuit Eskimo from Greenland.


Apolipoprotein E (apoE) plays a central role in lipoprotein metabolism thus affecting lipid homeosta-3sis in many tissues (Mahley, 1988). Three common isoforms have been described (apoE2, E3 and E4) encoded by the alleles e2, e3 and e4, respectively (Utermann et al., 1977; Davignon et al., 1988; Hallman et al., 1991). Recent studies have linked the e2 allele to type III hyperlipidemia (Utermann, 1987), and the e4 variant to coronary heart disease (CHD) (Cumming and Robertson, 1984; Davignon et al., 1988) and Alzheimer’s disease (AD) (Strittmatter et al., 1993; Saunders et al., 1993). Consequently, the frequency of apoE genotypes has been determined in several populations such as Caucasians. Blacks, Asians and North American Indians (Kamboh et al., 1990, 1991; Hallman et al., 1991; Kao et al., 1995; Sandholzer et al., 1995; Scheer et al., 1995; Benkmann et al., 1996; Kataoka et al., 1996). We determined the apoE allele distribution in five Amerindian tribes from the Brazilian Amazon region, and found that it differed from all other populations thus far studied, except for the Inuit Eskimo (Gerdes et al., 1996).


Populations sampled

The Amerindian sample comprised 121 individuals from five Brazilian Amazonian tribes: 23 Yanomami, 25 Wayana-Apalai, 26 Wayampi, 21 Arara and 26 Kayapo. The individuals studied were apparently unrelated, except for the Wayampi and the Arara among whom there are high inbreeding levels, making it difficult to select only unrelated individuals.

DNA analysis

DNA samples were obtained from leukocytes by phenol-chloroform extraction and ethanol precipitation and then PCR amplified, using primers and conditions described by Hixson and Vernier (1990). Genotypes were determined by restriction fragment length polymorphism (RFLP) analysis after disgestion with HhaI restriction enzyme and polyacrylamide gel electrophoresis. ApoE allele frequencies were determined by gene counting.


The frequencies of apoE alleles obtained for the Amerindians are compared with other populations in Table I. ApoE3 alelle had the highest frequency (0.8306), which is in accordance with frequencies described for Tyroleans, French Canadian Caucasians, Chinese and Alaskan natives (Hallman et al., 1991; Kao et al., 1995; Scheer et al., 1995; Robitaille et al., 1996). ApoE4 allele had a lower frequency among the Amerindians when compared to South African Khoi San, Papua-New Guineans, Australian aborigines and African blacks (Nigerians, Sudanese) (Kamboh et al., 1990, 1991; Hallman et al., 1991; Sandholzer et al., 1995; Benkmann et al., 1996) who are known to have high ApoE4 frequencies. The ApoE2 allele was absent in the Amazonian Amerindian populations, a fact that has also been described for an Inuit population residing in Greenland’s southeast coast (Gerdes et al., 1996), while a low ApoE2 frequency (0.02) has been found in Alaskan natives (Scheer et al., 1995). ApoE allele frequencies were homogeneous between the different tribes (Table II) except for the Wayampi, where the ApoE4 variant exhibited a frequency (0.423) compared to the highest reported for any human ethnic group to date (Kamboh et al., 1990, 1991; Hallman et al., 1991; Sandholzer et al., 1995; Benkmann et al., 1996). This difference cold be explained by isolation and genetic drift. A heterogeneous distribution of genetic polymorphic markers has been observed in these populations when studying other genetic systems, such as the a-globin gene haplotypes and several variable number of tandem repeats (VNTRs) (Zago et al., 1995, 1996).

Table I - Distribution of ApoE alleles in different human populations.


Caucasians (Tyroleans) (Hallman et al., 1991) 0.090

Blacks(Khoi San) (Sandholzer et al., 1995) 0.077

Asians (Chinese) (Kao et al., 1995) 0.076

Alaskans (Scheer et al., 1995) 0.020

Amazonian Amerindians (present study) 0.000

Table II - Distribution of ApoE alleles in five Amerindian populations (No. = number of chromosomes).







The frequencies of ApoE alleles in a population may have implications regarding CHD and AD prevalence. The ApoE2 allele is usually associated with lower total cholesterol (TC) and low density lipoprotein (LDL) levels and higher high density lipoprotein (HDL) levels, whereas the ApoE4 allele is usually linked to effects opposite to those described for the ApoE2 allele besides being associated with AD in several populations (Cumming and Robertson, 1984; Davignon et al., 1988; Hallman et al., 1991; Saunders et al., 1993; Strittmatter et al., 1993). Therefore, the absence of the ApoE2 allele as well as the high ApoE4 frequency among the Wayampi could play a role in the prevalence of these diseases in this population, a point which should be further investigated.


This work was partially supported by Conselho Nacional de Desenvolvimento Científico e Tecnológico (CNPq), PADCT and Financiadora de Estudos e Projetos (FINEP). Publication supported by FAPESP.

A determinação da distribuição do alelo ApoE em cinco tribos de índios sulamericanos revelou ausência do alelo ApoE2, acompanhada por freqüência alta do alelo ApoE3 e baixa do alelo ApoE4 na maioria das tribos, uma distribuição previamente relatada apenas para os esquimós Inuit da Groenlândia.


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