Interaction between ABO and haptoglobin systems in a Chilean population of mixed ancestry

Interaction between ABO and haptoglobin systems in a Chilean population of mixed ancestry

M. Acuña¹ and L. Eaton²

¹Departamento de Biología Celular y Genética, Facultad de Medicina, Universidad de Chile, Casilla 70061, Santiago 7, Chile. Send correspondence to M.A. Fax: [phone]. E-mail: [e-mail]

²Ecological Sciences Department, Faculty of Sciences, University of Chile, Chile.

ABSTRACT

In order to investigate the association between ABO blood groups and serum haptoglobin (Hp), we typed Hp and ABO blood groups in 288 children, who were selected at random among those who began their primary school in 1973 in the Northern Metropolitan area of Santiago, Chile. This region has an Amerindian component of 40% and a Caucasian component (principally Spanish) of 60%. Our results are in contrast with previous studies which have reported that Hp*1 varied among ABO groups in the following manner, O < A < B < AB, and where Hp*1 was significantly lower in group O individuals. In the present study, the order was A < O » B < AB. We found more A and less O individuals with allele Hp*2 and genotype Hp 2-2, and more Hp*1 among O individuals.

INTRODUCTION

Numerous authors have reported an association between ABO blood groups and serum haptoglobin (Hp). Ritter and Hinkelmann (1966) found a significant excess of the Hp 1-1 phenotype and a highly significant increase in Hp*1 allele frequency among the offspring of ABO-incompatible parents. This was in part confirmed by Kirk et al. (1970) and Kirk (1971). Vana and Steinberg (1975) used the same S-leut Hutterites data as Kirk (1971) and demonstrated that the ABO-Hp association cannot be explained by incompatibility, but that there is an unexplained association between the two systems. Mitchell and Eslick (1988) and Vana and Steinberg (1975) found that the allele Hp*1 occurs in a significantly lower proportion in individuals of group O, and that the frequency of this allele with respect to the ABO system has the following order, O < A < B < AB in the populations of Victoria, Australia and the Hutterites, respectively. Fröhlander (1985) reported a similar interaction in one county (Norrbotten) of Northern Sweden but not in another (Västerbotten). Bandopadhaya (1994) also found a significantly higher incidence of Hp*1 in the offspring born to ABO-incompatible mother-child combinations in comparison to offspring born to ABO-compatible combinations in Bengalee, India.

The present-day Chilean population has a high frequency of O (0.75) and a low frequency of Hp*1 (0.56) compared to European populations (Cavalli-Sforza and Bodmer, 1971; Cifuentes et al., 1988). This is a result of the origin of the Chilean people, principally from a mixture of Spanish (ABO*O = 0.65; Hp*1 = 0.41 (Campillo, 1976; Goedde et al., 1984)) and Amerindians (ABO*O = 0.98; Hp*1 = 0.75 (Matson et al., 1967; Llop and Rothhammer, 1988; Acuña et al., 1994)).

The northern metropolitan area of Santiago, Chile, has an Amerindian component of 40% and a Caucasian component (principally Spanish) of 60% (Acuña and Valenzuela, 1982). We only used individuals from this one sector, since it is known that the population of Santiago is heterogeneous for ABO and Hp frequencies in different sectors (Valenzuela and Harb, 1977; Valenzuela et al., 1987; Acuña, M., unpublished data).

MATERIAL AND METHODS

Blood samples were collected from 288 children, who were selected at random from all those who began their primary school in 1973 in the northern sector of Santiago. Further details of the sampling method may be found in Valenzuela et al. (1991). Samples were collected by venepuncture, and processed for ABO groups and Hp phenotype. ABO typing was performed using the internationally accepted standard methods; Hp typing followed the method of Smithies (1959) using the discontinuous buffer system of Poulik. G tests with Williams' correction (Sokal and Rohlf, 1995) were used for the examination of goodness-of-fit to the expected phenotypes.

RESULTS AND DISCUSSION

Allele frequencies for ABO were A = 0.1875; B = 0.0700 and O = 0.7425 (Table I). The observed phenotypic distribution was close to expected numbers under Hardy-Weinberg equilibrium conditions. The frequencies of Hp*1 and Hp*2 alleles were 0.5521 and 0.4479, respectively; Hp phenotypes were also in Hardy-Weinberg proportions. Although the two systems individually have equilibrium frequencies, a contingency analysis of the marginal values (Table I) demonstrated they were not independent. There was a significant interaction among the phenotypes (Table I) (G_adj = 16.08; 6 d.f.; P = 0.013).

The frequency of the Hp 2-2 genotype was significantly greater in blood group A than in non-A individuals (G_adj = 11.08; 2 d.f.; P = 0.004). This was also true for the two alleles of Hp: there was an excess of A individuals with Hp*2 (G_adj = 8.65; 1 d.f.; P = 0.003). Among O individuals there were also fewer Hp 2-2 than expected (G_adj = 7.66; 2 d.f.; P = 0.022).

Kirk et al. (1970) originally suggested that hemolytic problems in children due to ABO incompatibility might differentially affect Hp phenotypes in populations with high infant mortality. However, Kirk (1971) found similar relationships in populations without high infant mortality. Vana and Steinberg (1975) separated their data by ABO compatibility of parents, and showed that differences in Hp allele frequencies were independent of ABO compatibility.

Our results are in contrast with those of Vana and Steinberg (1975), who found that Hp*1 varied among ABO groups in Hutterites in the following manner: O < A < B < AB, and that Hp*1 was significantly lower in group O individuals. In our study, the order was A < O » B < AB (Table I), with marginally more Hp*1 among O individuals (G_adj = 3.027; 1 d.f.; P = 0.082).

We would have liked to have used meta-analysis to compare our results with previous studies, however, this method requires the null hypothesis that the studies are comparable, which is not true when the frequencies of the blood group alleles are different (Hong-Guang et al., 1997). The admixture of two groups which formed our population has resulted in allele frequencies quite different from those of other studies.

Since the Amerindian population has almost all O (0.98), it is obvious that very little interaction between ABO and Hp could have occurred before the arrival of Europeans. The Caucasian genes were incorporated at different rates in different strata (Thayer, 1919; Matson et al., 1967; Valenzuela et al., 1987); the greatest admixture with Amerindian genes occurred among the economically disadvantaged, who are the subjects of this study. Thus the ABO-Hp interaction which the Europeans brought has managed to maintain itself in spite of «dilution» with Amerindian O alleles. However, the interaction in this population takes a different form than those reported previously, with excess Hp 2-2 individuals who are A and few who are O.

The biological role of this association is not known; however, since the form the interaction takes is variable in different populations, we conclude that the ABO-Hp association must also be affected by other variable systems.

ACKNOWLEDGMENTS

We thank Dr. Carlos Valenzuela for authorizing use of the data base, and for helpful comments on an earlier draft of the manuscript.

RESUMO

Para investigar a associação entre os grupos sanguíneos ABO e a haptoglobina sérica (Hp), nós tipamos Hp e os grupos ABO em 288 crianças, que foram selecionadas ao acaso dentre aquelas que começaram o primeiro grau escolar em 1973 na área metropolitana norte de Santiago, Chile. Esta região tem um componente ameríndio de 40% e um componente caucasiano (principalmente espanhóis) de 60%. Nossos resultados contrastam com estudos prévios que relataram que Hp*1 variou entre os grupos ABO da seguinte maneira: O < A < B < AB, e onde Hp*1 foi significativamente menor em indivíduos do grupo O. No presente estudo, a ordem foi A < O » B < AB. Nós encontramos mais indivíduos A e menos O com alelo Hp*2 e genótipo Hp 2-2, além de mais Hp*1 entre os indivíduos do grupo O.

(Received March 12, 1997)

• Acuńa, M. and Valenzuela, C. (1982). Marcadores genéticos y estimación de mezcla en una población de Santiago, Chile. Arch. Biol. Med. Exp. 15: 169 (Abstract).
• Acuńa, M., Llop, E. and Rothhammer, F. (1994). Composición genética de la población chilena: Los Atacameńos de la Comuna de San Pedro de Atacama. Rev. Med. Chile 122: 1126-1133.
• Bandopadhaya, A.R. (1994). A mother-child combination analysis for ABO-Hp interaction in a Bengalee population. Hum. Hered. 44: 68-77.
• Campillo, F.L. (1976). Estudio de los Grupos Sanguíneos en la Población Espańola. Comunicación de la Real Academia de Medicina. Tomo XCII de los Anales, Cuaderno Tercero, Madrid.
• Cavalli-Sforza, L.L. and Bodmer, W.F. (1971). The Genetics of Human Populations. W.F. Freeman and Company, San Francisco.
• Cifuentes, L., Valenzuela, C., Cruz-Coke, R., Armanet, L., Lyng, C. and Harb, Z. (1988). Caracterización genética de la población hospitalaria de Santiago. Rev. Med. Chile 116: 28-33.
• Fröhlander, N. (1985). Haptoglobin-ABO association. Hum. Hered. 35: 198-200.
• Goedde, H.W., Hirth, L., Benckmann, H.G., Pellicer, A., Pellicer, T., Stahn, M. and Singh, S. (1984). Population genetic studies of red cell enzyme polymorphisms in four Spanish populations. Hum. Hered. 22: 552-560.
• Hong-Guang, X., Zhen-Hua, X., Dong-Sheng, O.Y., Yan, S., Dong-Liang, Y., Jun-Sheng, W., Xiang-Dong, Y., Song-Lin, H., Wei, W. and Ari, H. (1997). Meta-analysis of phenotype and genotype of NAT2 deficiency in Chinese populations. Pharmagenetics 7: 503-514.
• Kirk, R.L. (1971). A haptoglobin mating frequency, segregation and ABO blood-group interaction analysis for additional series of families. Ann. Hum. Genet. 34: 329-337.
• Kirk, R.L., Kinns, H. and Morton, N.E. (1970). Interaction between the ABO blood group and haptoglobin system. Am. J. Hum. Genet. 23: 384-389.
• Llop, E. and Rothhammer, F. (1988). A note on the presence of blood group A and B in pre-Colombian Southamerica. Am. J. Phys. Anthropol. 75: 107-111.
• Matson, G.A., Sutton, H.E., Etcheverry, R., Swanson, J. and Robinson, A. (1967). Distribution of hereditary blood groups among indians in South America. IV. In Chile. Am. J. Phys. Anthropol. 27: 157-194.
• Mitchell, R.J. and Eslick, C.J. (1988). Interaction between ABO and haptoglobin in a white Australian population. Hum. Hered. 38: 251-254.
• Ritter, H. and Hinkelmann, K. (1966). Zur balance des polymorphismus der haptoglobine. Humangenetik. 2: 21-24.
• Smithies, O. (1959). Zone electrophoresis in starch gel and its application to serum proteins. In: Anfinsen, C.B., Anson, M.L., Bailey, K. and Edsall, J.T., eds.). Advance Protein Chemistry Vol. 14. Academic Press, New York, pp. 65.
• Sokal, R. and Rohlf, J. (1995). Biometry 3rd edn. W.H. Freeman and Company, New York.
• Thayer, O.L. (1919). Elementos Étnicos que han Intervenido en la Población de Chile. Imprenta Litografía y Encuadernación, La Ilustración, Santiago, Chile.
• Valenzuela, C. and Harb, Z. (1977). Socioeconomic assortative mating in Santiago, Chile. Soc. Biol. 24: 225-233.
• Valenzuela, C., Acuńa, M. and Harb, Z. (1987). Gradiente sociogenético en la población chilena. Rev. Med. Chile 115: 295-299.
• Valenzuela, C., Avendańo, A. and Hard, Z. (1991). Association between Rh and plasma iron binding (transferrin). Hum. Genet. 87: 438-440.
• Vana, L.R. and Steinberg, A.G. (1975). Haptoglobin-ABO interaction: possible explanation for the excess of Hp1 among offspring of ABO incompatible matings. Am. J. Hum. Genet. 27: 224-232.

Publication Dates

• Publication in this collection
  01 Mar 1999
• Date of issue
  Dec 1998

History

• Received
  12 Mar 1997