Hum. Hcrcd. 27: 424-432 (1977)

The World Distribution of the Electrophoretic Variants of the Red Cell Enzyme Esterase D S. S. P a pih a and A. N ahar Department of Human Genetics, University of Newcastle upon Tyne, Newcastle upon Tyne

Key Worth. Esterase D • Electrophoretic variants • World distribution

Four biochemically and genetically distinct ‘esterase’ isoenzymes have been described in human red cells. Zymograms developed from the human red cell lysate using the conventional naphthyl ester show only the esterases A, B and C [26, 27]; rare variant forms of the first are known, but in neither of the others does any polymorphism occur in man. The fourth esterase, type D, has recently been described [8] in human tissues using an ester of fluores­ cent compounds. Although a variable degree of hydrolysis of the fluorescent ester is also brought about by the esterases A, B and C, the hydrolytic activity of esterase D and carbonic anhydrase I in red cells is greater and virtually specific to the four methyl umbelliferone esters. Initially, for the detection of the esterase D polymorphism several studies employed starch gel electro­ phoresis, but equally reproducible results of the esterase D pattern have been obtained using other supporting media such as cellulose acetate and agarose [4, 10]. Using these electrophoretic techniques three common phenotypes (Es D-l, Es D2-I and Es D-2) have been described, controlled by alleles Es Z)1and Es Dat a single locus, and the regularity of their inheritance has been well estab­ lished [3, 8, 23], In some populations, in addition to these two common autosomal alleles, two rare alleles Es D3 and Es D' have also been described [1,

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Abstract. The phenotypic variation in the esterase D phenotypes among 2,405 indi­ viduals in 14 samples from populations in Europe, Africa and Asia are reported. There exists a marked difference in esterase D allele frequencies in different continental regions. Comparison of the world population data so far available shows that esterase D is another useful genetic parameter for the study of population diversity.

425

Papiha/Nahar

2. 5], but the frequency of their occurrence is too slight to contribute appre­ ciable to the genetic diversity of populations. There are as yet relatively few population surveys to show the geographical variation in allele frequency in this system. The present communication adds data on esterase D distribution from our studies on material from 14 populations in different parts of the world and summarises present knowledge regarding the population variation of this system as distinguished electrophoretically.

Methods and Material In all, 2,405 rod cell lysates were examined for esterase D. The populations to which the samples related, the number of subjects tested, and the references in which other details of the material are given, are set out in table I. All red cell lysates were kept frozen at -30 C. Before the electrophoresis an aliquot of each lysate was treated with an equal volume of 20 him mercaptoethanol to eliminate any storage effect and to produce an accurate and clear electrophoretic pattern. The treatment

Table I. The populations and their respective sample size tested for esterase D variation by authors

Europe North-East England Belgium Italy Africa Uganda S W Asia Afghanistan Iru/iait sub-continent Punjab (Punjabis) Harayana (Jats) Delhi (Muslims) Himachel (Simla) Gujarat (Surat) Kerala ( Malayalis) Bangladesh (Bengali Muslims) Ceylon (Sinhalese) Tibetan (Simla and Darmsala) * Details of sample collection not yet published.

Number of specimens

Reference

583

16

166 90

* +

2 09

24

2 24

20

40



94

17

l(K)

17

128 283

♦ *

76

21

166

18

135

* *

114

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Population

426

P apiha/N ahar

of the red cell lysates with equal volumes of Cleland reagent (0.75% solution of Dithiothretiol) also produced satisfactory results like that with mercaptoethanol. Two different methods were used to characterise the esterase D phenotypes in the present samples. 605 specimens were analysed by high voltage electrophoresis using Tris-citrateborate and lithium hydroxide buffer pH 7.5. The buffer composition and electrophoretic conditions were as described by Köster et al. [10], For 1,800 red cell lysates horizontal starch gel electrophoresis was carried out using a citrate-phosphate buffer pH 5.9 as described by W elch [29]. Staining in both cases was carried out as described by H opkinson er al. [8] using 4-mcthyl umbelliferyl acetate as substrate. The few specimens in which there was any doubt about phenotypes were examined by both methods.

In all the 2,405 specimens only the three common phenotypes (I, 2-1, 2) were found (fig. 1). The numbers of the esterase D phenotypes observed in the 14 samples and the allele frequencies calculated from them, are listed in table 11; in none was there any departure from the phenotype numbers expected in Hardy-Weinberg equilibrium. For comparison, similar data from other populations of the world are also listed: in these only 2 samples show depar­ ture from Hardy-Weinberg equilibrium. Table II shows distinct geographical variation in the frequency of the Es Dallele, particularly associated with continental groups of populations. The African series resemble each other quite closely with gene frequencies of Es Di ranging from 0.055 to 0.110 and this narrow range of variation contrasts quite pronouncedly with the frequencies in South American Indian tribes, where Es D2 ranges from 0 to 0.0635 in frequency, though here the small size of some samples, and the isolated nature of the population from which they are drawn, are obviously factors. The European samples also show very striking resemblance to each other: the range of Es D2 frequency, from 0.050 toO.243, is inflated by the inclusion of a sample from Lapland, for when this is ex­ cluded the range only extends up to 0.155; in yet another system therefore is the distinction between the Lapps and other populations of western Europe established. The Far East, represented by four samples, shows considerable homogeneity, Es D2 ranging from 0.319 to 0.369, and the fact that this elevated frequency is characteristic of eastern Asians is indicated by a similar occur­ rence in other peoples of Mongoloid affinity, the Tibetans, Nepalese and Assamese. India occupies an intermediate position between the European levels and the east Asian, with Es Z)2 frequencies ranging from 0.171 to 0.274.

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Results am! Discussion

427

Only two geographically distinct regions - Great Britain and the Indian sub-continent - have been extensively studied as regards intra-regional dif­ ferences. In the 11 sub-samples from Great Britain, the sample from the Isle of Man showed a significantly elevated Es D- frequency by comparison with the remaining 10 samples, among which there was no significant variation in the numbers of the different phenotypes. The samples for India also showed no significant heterogeneity, whetheror not Ceylon and Bangladesh material was included with them, but the distinct difference of the frequencies from those in Nepalese and Tibetans demonstrates once again the importance of the Himalayas as a genetic barrier, already indicated in the AK and 6PGD gene frequencies [13, 15], and the presence of Mongoloid influences as indicated in so many ethnic variables. The position of Afghanistan, with a lower Es D2 frequency than India, may once again indicate the historical association of Af­ ghans with populations from the west. The Italian frequency of the EsD- allele at 5%, considerably lower than in the sample from Tuscany of Bargagna el at. [1], suggests some local variation within Italy, and may well reflect the fact that the present Italian sample comes from rather remote Alpine villages in which some effects of isolation may be expected. A comprehensive map of the allele frequency distribution is not yet pos­ sible, on account of the relatively small number of samples that is currently available for analysis, but some generalisations can nevertheless be drawn.

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Distribution of Esterase D

428

P apiha N ahar

Table II. Phenotypes of esterase D and the gene frequencies in different world populations

European Europeans English Northumberland North-east England South-east England Holy Island (England) South-west Scotland Isle of Wight Cumbria Isle of Man Irish (S. Ireland) Gypsies (GB) Bonn (W.Germany) North Germans West Germans Berlin (W. Germany) SW Germans Belgium Italy (Alpine villages) Newfoundland (W.Coast) Newfoundland (St.John) Tuscany (Italy) Copenhagen Lapland Swiss (Berne) Negroes Black (GB) Gambia Cameroons Uganda American Indians Makiritare Yanomama Parakanan Gorotire Kraho Moro Caingang Mapuche

Reference

Num­ Phenotype num­ Z* ber bers observed 2-1 2-2 tested 1-1

8 867 705 154 399 312 84 30 107 128 19 7 448 126 present study 583 22 906 711 182 7 126 102 22 829 7 673 149 7 1,505 1,197 288 67 7 51 15 226 89 7 320 186 144 38 30 30 122 30 153 24 561' 448 103 408 318 84 3 10 1.082 844 223 428 107 11 545 2 147 34 184' present study 166 133 31 present study 90 81 9 6 168 139 27 128 34 6 163 499' 365 125 1 26 1.392 1,118 259 136 80 46 30 774 558 174 23 8 29 30 present study

102 734 92 209

82 615 82 168

20 115 10 36

12 12 12 12 12 12 12 12

69 419 37 163 146 112 74 51

42 310 4 54 36 112 32 35

22 98 19 75 65 0 33 14

8 3 2 9 13 2 7 20 1 5 4 1 10 6 15 10 3 2 2 1 9 13 10 12

0.01 1.08 0.06 0.00 0.10 0.02 0.01 0.31 0.00 1.26 0.39 0.87 1.98 0.02 0.00 1.17 0.04 0.00 0.01 0.01 0.04 0.37 0.00 0.64 0.15

Gene frequency Es O' EsD-

0.902 0.887 0.911 0.876 0.885 0.897 0.902 0.891 0.873 0.845 0.877 0.895 0.889 0.882 0.883 0.884 0.891 0.894 0.950 0.908 0.890 0.856 0.896 0.757 0.867

0.098 0.113 0.089 0.124 0.115 0.103 0.098 0.109 0.127 0.155 0.123 0.105 0.109 0.118 0.117 0.116 0.109 0.106 0.050 0.092 0.110 0.143 0.104 0.243 0.133

0.07 0.902 0.098 4 0.56 0.916 0.084 0.03 0.945 0.055 5 0.18 0.890 0.110 5 II 14 34 45 0 9 2

1.44 0.90 0.09 0.71 1.64

0.768 0.857 0.365 0.561 0.469 1.000 0.09 0.655 0.01 0.824

0.232 0.143 0.635 0.439 0.531 -

0.345 0.176

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Population

429

Distribution of Esterase D Table // (continued) Population

Asia Indian (GB) Punjabi Punjabi Haryanvi Delhi ( Muslim) Himachali Gujarati Kerala (Malayan) Assamese Bangladesh (Bengali Muslim) Ceylon (Sinhalese) Nepalese Nepalese Tibetans Japanese (Western-Central Japan) Japanese (Tokyo) Ainu (Iburi Island) Ryukyuan (Okinawa Is.) South-west Asia Kuwait Iraq Afghanistan

Reference

8 7 present present present present present present 4

study study study study study study

present study present study 30 7 present study 9 14 14 14 7 19 present study

Num­ Phenotype num­ bers observed ber 2-1 2-2 tested l - t

Gene frequency EsD' EsD-

176 196 26 64 55 70 197 51 96

78 91 12 26 36 51 75 20 68

24 16 2 4 9 4 11 5 15

11.08 1.54 0.02 0.04 0.75 2.20 2.14 0.24 0.33

166 135 134 365 114

100 83 58 128 44

56 40 58 195 47

10 12 18 42 23

0.19 4.41 0.62 6.27 2.45

0.771 0.229 0.763 0.237 0.649 0.351 0.618 0.382 0.592 0.408

101 0.11 118 0.88 12 1.30 28 1.38

0.650 0.350 0.658 0.342 0.681 0.319 0.631 0.369

847 1,066 94 179 160 320 224

358 391 454 494 46 36 75 76 101

198 182

55 111 38

0.773 0.797 0.800 0.819 0.730 0.764 0.829 0.803 0.726

0.227 0.203 0.200 0.181 0.270 0.236 0.171 0.197 0.274

278 303 40 94 100 125 283 76 179

4 1.21 0.8032 0.197 11 0.91 0.792 0.208 4 0.08 0.897 0.103

Overall the geographical variation does not suggest any clinal component within any particular continent, but a strong variation between continents, with steep discontinuities in the intervening regions and intermediate values there where samples are available. Thus there is a clear increase in frequency of the Es D- allele as one moves from Europe into Asia, and as one moves from peninsular India into the area of Mongoloid influence. The apparent relict frequencies in the Lapps also testify to the strong ethnic component. Already it seems clear that the major component of variation in the esterase D

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* Comparing observed phenotype numbers with those expected from gene frequencies. 1 One further individual was of phenotype D 3-I.

430

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Table III. Es D- allele frequencies in various geographical regions

Africa Europe (excluding Lapps) Lapps South-west Asia South Asia Indian sub-continent Nepalis and Tibetans East Asia South American Indians

Number of subjects tested

Mean Es Dfrequencies

Range of variation of sample means

1,137 12,071 136 704

0.088 0.112 0.243 0.172

0.05-0.110 0.050-0.155 0.103-0.208

1,779 613 2,186 1,071

0.218 0.380 0.345 0.264

0.171-0.274 0.351-0.408 0.319-0.369 0.(XXV0.635

polymorphism is ethnic, strongly related to the continental groups (table III) to which the sampled population belongs, and this suggests that the frequen­ cies owe little to ecological factors.

A cknowledgments Acknowledgment is gratefully made to overseas colleagues Or. S arbjitS ing h ( Punjab), Dr. P. D. G ulati (Delhi), the late Dr. L. D. G arg (Himachel), Dr.K.. C. Shah (Surat), Dr. M. M. Islam (Bangladesh), Dr. K. P. A beyaratne (Ceylon), Dr. E. C. T. Ssebabi (Uganda), Dr. A. Leguebe (Belgium) and Dr. B. C hiarelli (Italy) for supplying the specimens. Thanks are due especially to Dr. D. F. R oberts for making available facilities for this work and for his help and guidance and to Dr.S.G. W elch for his kindness in confirming certain phenotypes.

References

the population of Tuscany. Humangenetik 29: 251-253 (1975). 2 Bender. K. und F rank , R.: Esterase-D-Polymorphismus: Darstellung in der Hoch­ spannungselektrophorese und Mitteilung von Allelehäufigkeiten. Humangenetik 23: 315-318 (1974). 3 Benkmann, H.G. and G oedde, H.W.: Esterase D polymorphism: gene frequencies and family data. Humangenetik 24: 325-327 (1974). 4 Benkmann, H.G. and G oedde, H.W.: Esterase D polymorphism in Assam by cellu­ lose acetate electrophoresis. Humangenetik 27: 343-345 (1975).

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1 Bargagna, M.: D omenici, R. and M orali, A.: Red cell esterase D polymorphism in

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5 Bhrg, K.; Schwarzfischer , P., and W ischerath, H.: Esterase D polymorphism: description of the new allele Esl D'1. Hum. Genet. 32: 81-83 (1976). 6 C arter, N .D .:A uton. J. A.; We.lch,S .G .; M arshall, H.W., and F raser, G .R .: Superoxide dismutase variants in Newfoundland - agene from Scandinavia...? Hum. Hcred. 26 : 4-7 (1976). 7 C artwright , R. A.: Bethel, I.L.: H argreaves, H.M.: Izatt, M., et at.: The red blood cell esterase D polymorphism in Europe and Asia. Hum. Genet. 33: 161-166 (1976). 8 H opkinson , D. A.; M estriner, M. A.: C urtner, J., and H arris, H.: Esterase D : a new polymorphism. Ann. hum. Genet. 37: 119-137 (1973). 9 Ishimoto, G.; K uwata, M., and F uiita , H.: Esterase D polymorphism in Japanese. Jap. J. hum. Genet. 19: 157-160 (1974). 10 K öster, B.; L eupold, H., and M auff, G.: Esterase D polymorphism: high-voltage agarose gel electrophoresis and distribution of phenotypes in different European populations. Humangenetik 28 : 75-78 (1975). 11 M artin , W. und O rr, A .: Polymorphismus der menschlichen Erythrozyten. Esterase D. Phänotypenverteilung und Genfrequenzen in Berlin (West). Blut 30: 299-301 (1975). 12 M estriner, M.A.: Salzano, F. M.; N eel, J. V., and A yres, M.: Esterase D in South American Indians. Am. J. hum. Genet. 28: 257-261 (1976). 13 M ourant A.E.; G odber, E. M.; Kopec, A.C.: L ehmann, H.; Steele P. R., and T ills, D.: The hereditary blood factors of some populations in Bhutan. Anthropologist, suppl., pp.29-43 (1968). 14 O moto, K.; Aoki, K., and H arada, S.: Polymorphism of esterase D in some popu­ lation groups in Japan. Hum.Hered. 25: 378-381 (1975). 15 P apiha , S.S.; R oberts, D .F .; W ig , N .N ., and S ingh , S.: Red cell enzyme poly­ morphisms in Punjabis in North India. Am J. phys. Anthrop. 37: 293-300 (1972). 16 P apiha , S.S. and R oberts, D. F .: Haptoglobin distribution in north-east England. Ann. hum. Biol, (in press, 1976). 17 P apiha , S. S.: R oberts, D. F., and G ulati, P. D .: Some erythrocyte enzyme and serum protein systems in 2 communities of north-west India. Hum. Biol. 48: 323-336 (1976). 18 Papiha , S.S.: R oberts, D. F.; A li, S.G. M., and Islam, M. M.: Some hereditary blood factors of the Bengali muslim of Bangladesh (red cell enzymes, haemoglobins and serum protein). Humangenetik 28: 285-293 (1975). 19 P apiha , S. S. and A l-A gidi, S. K .: Esterase D and superoxide dismuiase polymorphism in Iraq. Hum.Hered.26: 394-400(1976). 20 Papiha , S.S.; R oberts, D. F.,and R ahimi, A .G .: Genetic polymorphisms in Afghani­ stan. Ann. hum. Biol, (in press, 1977). 21 P apiha , S.S. and W astell, H.J.: Transferrin variants in the Indian subcontinent. Humangenetik 21: 69-73 (1974). 22 P arkin , B. and Adams, E.G.: The typing of esterase D in human blood stains. Med. Sei. Law 15: 102-105 (1975). 23 P flugshaupt, R.; Scherz , R., and Butler, R.: Polymorphism of human red cell adenosine deaminase, esterase D, glutamate pyruvate transaminase and galactose Iphosphate-uridyltransferase in the Swiss population. Hum. Hered. 26: 161-166 (1976). 24 R ittner, C.H. and M üller, G.: Esterase D: some population and formal genetical data. Hum. Hered. 25: 152-155 (1975).

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Dr. S. S. Papiha, Department of Human Genetics, University of Newcastle upon Tyne, 19 Claremont Place, Newcastle upon Tvnc NE2 4AA (England)

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25 R oberts, D. F .: P apiha , S.S., and Ssebabi, E .C .T .: Red cell isoenzymes in Easi Africa. Hum. Biol, (in press, 1976). 26 SOrensen, S. A. and F enger, K.: Gene frequencies and linkage data in man. Hum. Hered. 26: 90-94(1976). 27 T ashian, R.E.: Multiple forms of esterases from human erythrocytes. Proc.Soc.exp. Biol. Med. 108: 364(1961). 28 T ashian, R.E.: The esterases and carbonic anhydrases in human erythrocytes; in Y unis Biochemical methods in red cell genetics, pp. 307-336 (Academic Press, New York 1969). 29 W elch, S.G.: Red cell esterase D in Gambia. Humangenctik 21: 365-367 (1974). 30 W elch. S.G. and Lee, J.: The population distribution of genetic variants of human esterase D. Humangenctik 24: 329-331 (1974).

The world distribution of the electrophoretic variants of the red cell enzyme esterase D.

Hum. Hcrcd. 27: 424-432 (1977) The World Distribution of the Electrophoretic Variants of the Red Cell Enzyme Esterase D S. S. P a pih a and A. N ahar...
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