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Genetic differences between Mestizo populations of Bolivia and Peru

Diferencias genéticas entre poblaciones mestizas de Bolivia y Perú
Différences génétiques entre les populations métisses de Bolivie et du Pérou
Jorge Cervantes
p. 213-222

Resúmenes

Existe escasa información acerca del fondo genético de las poblaciones de Perú y Bolivia. Estudios han mostrado que los mestizos presentan varios alelos del sistema mayor de histocompatibilidad originalmente descritos en tribus amerindias genéticamente aisladas, y que los mestizos de Perú y Bolivia están genéticamente cercanamente relacionados.
Mediante la técnica de transferencia de línea reversa, se realizó la tipificación de alelos de histocompatibilidad de Clase I (HLA-A, HLA-B, HLA-Cw) así como de Clase II (HLA-DRB1 y HLA-DQB1) en 57 mestizos bolivianos. Los sujetos provinieron mayormente de La Paz (la ciudad principal en los Andes Bolivianos), además de otras tres ciudades importantes situadas en el Valle Central Boliviano (Sucre, Tarija y Tupiza).
La comparación de la frecuencia de los alelos de los mestizos bolivianos con datos disponibles de la literatura acerca de mestizos peruanos, reveló que los alelos de Clase I HLA-Cw*01, y B*40 se encontraban en mayor proporción en el grupo de mestizos peruanos (Chi-cuadrado = 4.87 p<0,05; y chi-cuadrado = 7,56 p<0,01 respectivamente). Con respecto a los alelos de clase II, HLA-DRB1*1101 y DRB1*1302 se encontraron en mayor frecuencia en los mestizos peruanos (Chi-cuad = 5,12 p<.05 ;y chi-cuad = 3,8 p = 0.05 respectivamente), mientras que el alelo HLA-DQB1*0402 fue significativamente mayor en los mestizos bolivianos (Chi-cuad = 47,2 p<.0001).
Las diferencias en las frecuencias de alelos encontradas, y la ausencia o presencia de algunos alelos en cualesquiera de los grupos, puede deberse a un grado mayor de mixtura en los mestizos de Bolivia con grupos étnicos andinos, y/o menos rasgos rurales y mayor mixtura caucásica en los mestizos peruanos reportados en la literatura.
Estos hallazgos podrían tener un impacto con respecto a la eficacia de formas modernas de inmunización a través de vacunas de ADN en población andina, y en la identificación de riesgo para ciertas condiciones médicas.

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Entradas del índice

Keywords :

Mestizo, HLA, allele, DNA

Palabras claves :

Mestizo, histocompatibilidad, alelo, ADN
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Texto completo

Introduction

1Bolivia and Peru are neighboring South American Andean countries, sharing geographically the Altiplane and the Titicaca Lake (the highest lake in the world). Besides its geographic connection, cultural, ethnic and linguistic liaisons are present between both countries since the Inca Empire times.

2Bolivia is one of the less populated countries in South America. Ethnic groups present in this country are: Quechua, Aymara, Mestizo, White, and Guarani. Previous reports have shown that Peruvian and Bolivian mestizo (i.e Mixed, of predominantly Native American Ancestry) are closely genetically related (de Pablo et al., 2000).

3The human major histocompatibility complex (MHC) (termed HLA, for human leukocyte antigen) comprises a family of genes that control immune response to pathogens, graft acceptance or rejection (i.e. transplant “compatibility”), and tumor surveillance. Its importance has been recognized by the award of the Nobel Prize to Doherty and Zinkernagel in 1996. The MHC has been the focus of interest since the past decades, as its extensive polymorphism defines a unique genetic fingerprint of an individualÅfs immune system, that is why HLA typing applications are not confined to medicine and medical research (transplantation, and disease association), it is also useful in paternity testing, in which is an informative tool for excluding parentage in cases of false accusation (Bryant, 1994), and in molecular anthropology giving scientific support to generate hypothesis about patterns of human evolution and migration (Apple & Erlich, 1996) .

4Originally described by Goran in the 1930's, the MHC is encoded on the short arm of the chromosome 6 in humans and includes at least 200 genes. The complex is divided into three regions: Class II (HLA-DR, -DP and -DQ genes), class III (which includes genes encoding complement and tumor necrosis factor), and class I (HLA-A, -B, -C, -E, -H, -G and -F genes) (Moss et al., 1999).

5Data on the genetic background of Peruvian and Bolivian populations is somehow still scarce. As studies have shown that mestizos (i.e. Mixed, of predominantly Native American Ancestry) (IHWG, 2002), are closely genetically related, we performed HLA class I and HLA class II allele typing in 57 Bolivian mestizos and compared their allele frequencies with data available from the literature from Peruvian mestizos (de Pablo et al., 2000; Castro et al., 2001; Seclen, 1996).

1. Subjects and Methods

1. 1. Subjects

6Fifty seven (57) Bolivian mestizosmestizos. Most of the study subjects came from La Paz, the main city in the Bolivian Altiplane (located between 3150 and 4100 meters above the sea level), and from three other important cities in the Bolivian Central Valley (Sucre, Tarija and Tupiza).

1. 2. Samples

7After obtaining informed consent, peripheral blood samples were collected. Sera and peripheral blood lymphocytes (PBL) were separated and cryopreserved as described elsewhere (Katahira et al., 1995)

1. 3. HLA typing

8Chromosomal DNA was extracted from the cryopreserved peripheral blood lymphocytes by the guanidine-HCl procedure (SMITEST EX-R&D, Sumitomo Metal Industry Japan). HLA typing for Class I (HLA-A, HLA-B, HLA-Cw) as well as Class II (HLA-DRB1 and HLA-DQB1) alleles was performed by a PCR-reverse line blot assay (Bugawan et al.,1994) (Dynal RELITMSSO, Dynal Biotech Ltd, U.K.).

1. 4. Statistical Analysis

9The Chi-square or Fisher's exact test, where appropiate, was used for comparison of allele frequencies between Bolivian and Peruvian mestizos. Tests were run using SPSS (Statistical Package for the Social Sciences) software, version 7.5 (SPSS Inc. 1989-1996).

2. Results

10Comparison of the allele frequencies of Bolivian mestizos with available data from Peruvian mestizos (de Pablo et al., 2000; Castro et al., 2001; Seclen, 1996), revealed that Class I HLA-Cw*01, and B*40 alleles were higher in the Peruvian mestizo group (Chi-sq = 4,87 p<0,05; and chi-sq = 7,56 p<0,01 respectively) (Table 1). Regarding Class II alleles, HLA-DRB1*1101 and DRB1*1302 alleles were higher in Peruvian mestizos (Chi-sq = 5,12 p<.05; chi-sq = 3,8 p = 0,05 respectively), while HLA-DQB1*0402 was significantly higher in Bolivian mestizos (Chi-sq = 47,2 p<.0001) (Tables 2 and 3).

3. Discussion

11Some indigenous populations (Native Americans for example) show a very restricted diversity of HLA alleles, which reflects a population bottleneck in the founding of these groups (Apple & Erlich, 1996). In contrast, African populations contain the most diverse set of HLA class II alleles and haplotypes, (i.e. groups of closely linked alleles) consistent with the hypothesis that modern humans arose from an ancestral African population.

12It has been reported that Peruvian and Bolivian mestizos are closely genetically related (de Pablo et al., 2000). Even though most of South American countries like Peru share a “Spanish Caucasoid genetic pool” (Serrano-Rios et al., 1999), HLA differences found here might be due to the fact that our mestizo population came from subjects participating in a field study, while those reported in the literature from Peru are composed mainly of people attending social security Hospitals, with probably less rural traits and more white (Caucasian) admixture, and/or a higher grade of admixture with Andean ethnic groups in the mestizos from Bolivia. It is interesting to see for example absence of DRB1*1602 (a well known Amerindian allele) in the group of Peruvian mestizos reported form Arequipa (de Pablo et al., 2000) (see Table 2).

Table 1 - HLA Class I allele frequencies in Peruvian (Arequipa) and Bolivian mestizos

 

Peruvian mestizo

Bolivian mestizo

 

(n=148)

(n=57)

 

296 alleles

114 alleles

HLA Class I alleles

n

AF (%)

n

AF (%)

A*01

12

4.1

2

1.8

A*02

162

54.5

54

47.4

A*03

12

4.0

6

5.3

A*11

13

4.4

0

0.0

A*23

6

2.0

3

2.6

A*24

31

10.4

13

11.4

A*26

3

1.0

5

4.4

A*29

8

2.7

2

1.8

A*30

5

1.7

2

1.8

A*31

12

4.0

10

8.8

A*32

6

2.0

1

0.9

A*36

1

0.3

0

0.0

A*66

2

0.7

0

0.0

A*68

20

6.8

15

13.2

A*69

1

0.3

1

0.9

A*80

2

0.7

0

0.0

Cw*01

41

13.3 a

9

7.9

Cw*02

4

1.4

2

1.8

Cw*03

27

8.8

9

7.9

Cw*04

115

37.4

44

38.6

Cw*05

10

3.4

2

1.8

Cw*06

7

2.4

5

4.4

Cw*07

34

11.1

16

14.0

Cw*08

24

7.9

11

9.6

Cw*12

6

2.0

3

2.6

Cw*15

21

6.7

12

10.5

Cw*16

6

2.0

1

0.9

B*05

0

0.0

7

6.1

B*07

7

2.4

2

1.8

B*08

7

2.5

2

1.8

B*13

2

0.7

1

0.9

B*14

5

1.7

1

0.9

B*15

31

10.6

7

6.1

B*18

2

0.7

1

0.9

B*22

1

0.3

0

0.0

B*27

2

0.7

1

0.9

B*35

102

34.5

44

38.6

B*37

1

0.3

0

0.0

B*38

4

1.4

2

1.8

B*39

14

4.7

7

6.1

B*40

31

10.6 b

4

3.5

B*41

0

0.0

1

0.9

B*42

1

0.3

0

0.0

B*44

18

6.1

4

3.5

B*45

3

1.0

1

0.9

B*46

1

0.3

0

0.0

B*47

2

0.7

0

0.0

B*48

24

8.2

7

6.1

B*49

2

0.7

2

1.8

B*50

2

0.7

2

1.8

B*51

24

8.2

16

14.0

B*52

2

0.7

1

0.9

B*53

2

0.7

0

0.0

B*55

2

0.7

0

0.0

B*57

1

0.3

1

0.9

B*58

1

0.3

0

0.0

AF = Allele frequency
a Statistical significance determined by a Chi-square test. HLA-Cw*01allele frequency higher in Peruvian mestizos compared to Bolivian mestizos (Chi-sq= 4.87 p<0.05)
b Statistical significance determined by a Chi-square test. HLA-B*40 allele frequency higher in Peruvian mestizos compared to Bolivian mestizos (Chi-sq= 7.56 p<0.01)

Table 2 - HLA Class II allele frequencies in Peruvian (Arequipa) vs. Bolivian mestizos

Peruvian mestizo

Bolivian mestizo

(n=148)

(n=57)

296 alleles

114 alleles

HLA class II alleles

n

AF (%)

n

AF (%)

DRB1*01

4

1.4

2

1.8

DRB1*02

16

5.1

0

0.0

DRB1*0301

17

5.4

3

2.6

DRB1*04

55

17.9

31

27.2

DRB1*0701

14

4.6

5

4.4

DRB1*08

58

18.8

29

25.4

DRB1*0901

54

17.6

12

10.5

DRB1*1001

2

0.7

1

0.9

DRB1*1101

15

4.9a

1

0.9

DRB1*13

19

6.3

7

6.1

DRB1*1402

42

13.8

14

12.3

DRB1*1501

0

0.0

1

0.9

DRB1*1602

0

0.0

8

7.0

DQB1*0201

9

6.9

7

6.1

DQB1*0301

36

27.7

24

21.1

DQB1*0302

28

21.5

33

28.9

DQB1*0303

23

17.7

11

9.6

DQB1*0304

0

0.0

1

0.9

DQB1*0401

11

8.5

0

0.0

DQB1*0402

6

4.6

29

25.4b

DQB1*0501

5

3.8

3

2.6

DQB1*0503

1

0.8

0

0.0

DQB1*0601

2

1.5

0

0.0

DQB1*0602

2

1.5

2

1.8

DQB1*0603

1

0.8

2

1.8

DQB1*0604

6

4.6

2

1.8

AF = Allele frequency
a Statistical significance determined by a Chi-square test. HLA-DRB1*1101 allele frequency higher in Peruvian mestizos compared to Bolivian mestizos (Chi-sq= 5.12 p<0.05)
b Statistical significance determined by a Chi-square test. HLA-DQB1*0402 allele frequency higher in Bolivian mestizos compared to Peruvian mestizos (Chi-sq= 47.3 p<0.0001)

Table 3 - HLA Class II allele frequencies in Peruvian (Lima) vs. Bolivian mestizos

Peruvian mestizo

Bolivian mestizo

(n=65)

(n=57)

130 alleles

114 alleles

HLA Class II alleles

n

AF (%)

n

AF (%)

 

DRB1*0101

3

2.3

2

1.8

DRB1*0102

2

1.5

0

0.0

DRB1*0301

3

2.3

3

2.6

DRB1*0302

1

0.8

0

0.0

DRB1*04

40

30.8

31

27.2

DRB1*0701

3

2.3

5

4.4

DRB1*08

18

13.8

29

25.4

DRB1*0901

18

13.8

12

10.5

DRB1*1001

0

0.0

1

0.9

DRB1*1101

6

4.6

1

0.9

DRB1*1103

2

1.5

0

0.0

DRB1*1104

2

1.5

0

0.0

DRB1*1301

0

0.0

2

1.8

DRB1*1302

7

5.4a

1

0.9

DRB1*1303

1

0.8

2

1.8

DRB1*1304

3

2.3

0

0.0

DRB1*1305

1

0.8

1

0.9

DRB1*1320/29

0

0.0

1

0.9

DRB1*1402

11

8.5

14

12.3

DR2

9

6.9

9

7.9

DQB1*0201

9

6.9

7

6.1

DQB1*0301

36

27.7

24

21.1

DQB1*0302

28

21.5

33

28.9

DQB1*0303

23

17.7

11

9.6

DQB1*0304

0

0.0

1

0.9

DQB1*0401

11

8.5

0

0.0

DQB1*0402

6

4.6

29

25.4

DQB1*0501

5

3.8

3

2.6

DQB1*0503

1

0.8

0

0.0

DQB1*0601

2

1.5

0

0.0

DQB1*0602

2

1.5

2

1.8

DQB1*0603

1

0.8

2

1.8

DQB1*0604

6

4.6

2

1.8

AF = Allele frequency
a Statistical significance determined by a Chi-square test. HLA-DRB1*1302 allele frequency higher in Peruvian mestizos compared to Bolivian mestizos (Chi-sq = 3,8 p = 0,05)

13Ethnic distribution in Bolivia comprises mestizo (Mixed) almost 38%, followed by a significant percentage of Quechua (34%) and Aymara (22%) populations, and other ethnicities found in the lowland (1,5 %). The study of whether or not similar differences between other ethnic groups present in both countries occur is warranted. A study of ethnic identity at a genetic level of Quechua Andean populations of Bolivia and Peru is planned in the near future by this laboratory.

14The MHC contributes significantly to the genetics human disease, as MHC contribute to the genetic susceptibility to autoimmunity, cancer and infectious diseases (Howard et al., 1999). Correlations of diseases with HLA antigen frequency have been the subject of considerably research, and HLA is found to be associated with several diseases (Bryant, 1994). Particular HLA alleles and haplotypes found in Hispanic groups and Mestizo populations have been reported associated with clinical (Castro et al., 1996, Gil-Carrasco et al., 1999), infectious (Fujiyoshi et al., 1995; Maciag et al., 2000; Silva et al., 1999; Apple et al., 1994; Apple et al., 1995) autoimmune (García-González et al., 1999) or metabolic diseases (Serrano-Ríos et al., 1999; Seclen et al., 1996). I recently made a preliminary report on a particular Amerindian allele conferring risk to infection with the human papillomavirus, responsible of causing cancer of the uterine cervix in women (Cervantes et al., 2002).

15The importance of our findings may have an impact regarding efficacies of modern forms of immunization by means of DNA vaccines (which interact with the HLA-class molecules) (Mc Donell & Askari, 1996), as well as in the identification of groups at risk for certain medical conditions in Andean populations.

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Para citar este artículo

Referencia en papel

Jorge Cervantes, « Genetic differences between Mestizo populations of Bolivia and Peru », Bulletin de l'Institut français d'études andines, 32 (1) | 2003, 213-222.

Referencia electrónica

Jorge Cervantes, « Genetic differences between Mestizo populations of Bolivia and Peru », Bulletin de l'Institut français d'études andines [En línea], 32 (1) | 2003, Publicado el 08 abril 2003, consultado el 22 julio 2017. URL : http://bifea.revues.org/6500 ; DOI : 10.4000/bifea.6500

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Autor

Jorge Cervantes

Department of Virology. Kagoshima University, Japan. E-mail:jorge-c@m3.kufm.kagoshima-u.ac.jp

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