Distribution of HLA antigens in Polish and German populations in Milwaukee Wisconsin.код для вставкиСкачать
Distribution of HLA Antigens in Polish and German Populations in M i lwaukee, Wisconsin JOAN c. STEVENSON AND RENE J. DUQUESNOY I Department of Anthropology, University of Wisconsin-Milwaukee and The Milwuukee Blood Center, Ine., Milwaukee, Wisconsin 53201 K E Y WORDS Poles Germans . HLA . Haplotype association . Slavonic a - Gametic ABSTRACT Gene and haplotype frequencies for HLA-A and HLA-B antigens were determined in Milwaukee blood donors of German and Polish descent. Gene frequencies for A25 and B18 were significantly higher in Poles than in Germans. Significant gametic associations were noted for Al-B8, A29-Bl2 and AW30-B13 in both populations. Gametic association for A3-B7 was only found in Germans, while the A25-Bl8 haplotype frequency was significantly increased in Poles. Since the latter haplotype has also been found in Yugoslavs, Ukrainians and Czechs, it is possible that A25-Bl8 represents a Slavonic marker. Histocompatibility testing or HLA typing has been shown to be a powerful tool for anthropological analysis of human populations (Dausset and Colombani, '72). The multiallelic HLA system is the most polymorphic genetic system presently known. Most extensively described have been the products of HLA-A and HLA-B genes; more than 20 antigens controlled by each of these genes have been recognized (Kissmeyer-Nielsen,'75). Although HLA information has been reported on some Central European groups (Albert et al., '72; Bertrams et al., '71; Gleichman, '74; Kastelan e t al., '74; Menzel and Richter, '72; Lenhart et al., '77; Singal and Bhargava, '75) no articles have been published on Poles, and available data on Germans do not include some of the more recently discovered HLA antigens. This paper presents results of an analysis of HLA-A and HLA-B antigens in blood donors in Milwaukee, Wisconsin, who were of Polish or German descent. The majority of Poles in Milwaukee arrived between 1880 and 1900 from what was then Austrian and Russian territory, (Milwaukee Writer's Project, '47). The periods of greatest German emigration to Wisconsin were between 1846 and 1854 and from 1881 to 1884 (Faust, '27). Most Milwaukee Germans came AM. J . PHYS. ANTHROP. (1979)50: 19-22. from Rhenish Prussia, Bavaria, Luxenburg, Baden and Saxony, (Gregory, '31). METHODS Serum samples of Milwaukee Poles and Germans were collected a t the Milwaukee Blood Center from unrelated donors of mixed ages and both sexes who indicated on questionnaires that all four grandparents were of direct Polish or German descent. The standard NIH microlymphocytotoxicity test (Terasaki's technique modified) was used to determine the HLA type of the blood donors in this study (Ray et al., '76). The following HLA specificities were identified: Al, A2, A3, A9, A10, A l l , AW23, AW24, A25, A26, A28, A29, AW30, AW31, AW32 and AW33 a t the A locus, and, B5, B7, B8, B12, B13, B14, B15, BW16, B17, B18, BW21, BW22, B27, BW35, B37 and B40 a t the B locus. Gene frequencies were calculated by the formula g = 1 where g is the gene frequency and p the phenotype frequency obtained by direct counting. Statistical significance of gametic association (linkage disequilibrium) between A and B locus antigens were ' Reprint requests t o : Rene J. Duquesnoy, Ph.D.,Director, Research and Development, Milwaukee Blood Center, Inc., 1701 West Wisconsin Avenue, P.O. Box lO-G, Milwaukee, Wisconsin 53201. 19 20 JOAN C. STEVENSON AND RENE J. DUQUESNOY TABLE 1 Gene frequencies of HLA antigens in Milwaukee blood donors of Polish and German descent Milwaukee Poles n = 175 HLA antigens Milwaukee Germwns n = 190 analyzed from 2 x 2 comparisons with the Chi Square test using Yate's correction (CavalliSforza and Bodmer, '71). Coefficients of association between A and B locus antigens were calculated by the formula r HLA-A locus A1 A2 A3 A9 A10 All Awl9 AW23 AW24 A25 A26 A28 A29 AW30 AW31 AW32 AW33 Blank A 0.1514 0.2788 0.1184 0.1324 0.1088* 0.0558 0.1073 0.0172 0.1152 0.0544** 0.0544 0.0348 0.0289 0.0468 0.0086 0.0202 0.0028 0.0123 HLA-B locus B5 B7 B8 B12 (BW44) B13 B14 B15 BW16 B17 B18 BW21 BW22 B27 BW35 B37 B40 BW45 Blank B 0.0588 0.0992 0.0928 0.0992 0.0649 0.0202 0.0558 0.0438 0.0528 0.0583*** 0.0269 0.0260 0.0680 0.1087 0.0028 0.0586 0.0000 0.0632 = x L is the Chi Square value &whereby and the N is the total number of samples tested. (Cavalli-Sforza and Bodmer, '71). Delta values of gametic association were calculated as 0.1324 0.3233 0.1602 0.1092 0.0614* 0.0402 0.0951 0.0212 A = - d- - - b + d c + d n n n where a, b, c, d are the respective frequencies ofthe + f , + -, - + and - - phenotypes and b c d (Ceppellini, '67). n =a Haplotype frequencies were calculated as the sum of the A values of gametic association and the product of the relevant gene frequencies (Mattiuz, et al., '70). 0.0880 + + + 0.0239** 0.0375 0.0293 0.0234 0.0320 0.0105 0.0293 0.0000 0.0488 RESULTS Gene frequencies for HLA-A and B antigens in Milwaukee blood donors of German and Polish descent are shown in table 1. Blank A and B frequencies indicate total gene frequencies of serologically undetectable products of HLA-A and HLA-B loci, respectively. The distribution of gene frequencies for HLA antigens was similar in both population groups except for A10, A25 and B18, which were significantly higher in Poles than in Germans. The gene frequencies for A l l , A26, AW30, B13, BW16, BW21 and B27 were somewhat higher and those of A3, B7, B8 and B12 were lower in Poles than in Germans, but the differences were not statistically significant. In these two population groups, five gametic associations were found in statistically significant (p < 0.01) linkage disequilibrium (table 0.0681 0.1204 0.1114 0.1477 0.0375 0.0159 0.0737 0.0320 0.0485 0.0185*** 0.0185 0.0132 0.0485 0.1055 0.0028 0.0794 0.0026 0.0058 * p < 0.05. ** p < 0.01. *** p < 0.001 TABLE 2 Haplotype frequencies (HFI with significant delta ualues (d ! and association coefficients (rl Milwaukee Poles and Germans Poles Haplotype HF Al-B8 A3-B7 A25-Bl8 A29-Bl2 AW30-Bl3 0.166 0.074 0.046 0.046 0.034 Germans _-__ A 0.116*** ns 0.034*** 0.035"' 0.023' LR r HF 0.66 ns 0.32 0.36 0.21 0.137 0.121 0.011 0.037 0.021 Significant levels of gametic associations are indicated with aaterisks * p < 0.01. ** p < 0.001. *** p < 0.0001. ns, not significant. A 0.085**' 0.054** na 0.025* 0.016* r 0.47 0.27 ns 0.22 0.22 21 HLA ANTIGENS IN POLES AND GERMANS 2). The association between A1 and B8 was most extreme in both Poles and Germans as evidenced by high A values (0.116 and 0.085) and association coefficients (r = 0.66 and r = 0.47). Haplotypes A 2 9 - B l 2 and AW30-Bl3 were also found in significant linkage disequilibrium in both populations. In contrast, the haplotype A25-Bl8 had signficant h and r values in Poles (P < 0.0001) but not in Ger- mans. The reverse situation was observed for A3-B7 which showed significant linkage disequilibrium only in Germans (p < 0.001). DlSCUSSION The results of this study show similar but not identical distributions of HLA antigens in Milwaukee Poles and Germans. They are comparable to data obtained with other major Eu- TABLE 3 Gene frequencies o f HLA antigens in Central and Eastern European populations Slavs Germans HLA antigens HLA-A locus A1 A2 A3 A9 A10 All Awl9 AW23 AW24 A25 A26 A28 A29 AW30 AW31 AW32 AW33 Blank A HLA-B locus B5 B7 B8 B12 B13 B14 B15 BW16 B17 B18 BW21 BW22 B27 BW35 B37 B40 BW41 BW45 BW53 Blank B Berlin n = 600 Essen ' n = 255 Munich D = 442 Hannover n = 386 0.1585 0.2933 0.1417 0.0982 0.0844 0.0478 0.1905 0.3283 0.1495 0.1406 0.0496 0.0562 0.144 0.260 0.156 0.091 0.059 0.063 0.084 0.1408 0.3021 0.1377 0.1287 0.0518 0.0573 0.1088 - - - 0.039 0.033 0.0249 0.0699 - - 0.0435 0.0258 - - - Czechs n = 267 Yugublavs n - 178 0.1291 0.2656 0.1454 0.1131 0.1036 0.0608 0.0351 0.051 0.0389 0.1531 0.2765 0.1274 0.1306 0.0752 0.0562 0.0764 0.0214 0.1092 0.0174 0.0578 0.0436 0.0243 0.0139 0.0139 0.0243 - - - - - - - - 0.0519 0.0283 - 0.0068 - 0.1326 0.0596 0.083 0.1015 0.0611 0.0350 0.0709 0.1150 0.1084 0.1169 0.0305 0.0248 0.0549 0.0569 0.1668 0.1376 0.1345 0.0508 0.0448 0.0376 0.0782 0.1483 0.0924 0.1392 0.0303 0.0369 0.0924 0.0619 0.0435 0.0135 0.0455 0.0735 0.0217 0.0297 0.0566 0.068 0.152 0.100 0.122 0.040 0.017 0.063 0.017 0.039 0.042 0.025 0.016 0.037 0.080 0.0519 0.1005 0.0789 0.0912 0.0284 0.0198 0.0548 0.0256 0.0342 0.0881 0.0430 0.0441 0.0608 0.1553 0.071 0.0768 0.0805 0.1178 0.0955 0.0985 0.0521 0.0169 0.0564 0.0347 0.0424 0.0462 0.0191 0.0323 0.0822 0.1052 0.0019 0.0626 0.0095 - - - 0.2133 ' M e n d and Richter, '72. ' Bertram8 et al., '71. Albert et al., '72. ' Gleichman, '74. ' lenhart et al., '77. Kastelan et al.. '74. - + ' Singal and Bhargava. '75. - - - - - - 0.0463 0.111 - 0.0289 0.0026 0.0259 0.0065 0.0410 0.0782 - - 0.1353 - 0.0462 Canadian Ukrainians n - 93 0.18 0.33 0.06 0.13 0.11 0.06 0.08 0.01 0.11 0.06 0.04 0.04 0.01 0.02 0.02 0.02 0.01 0.01 0.14 0.10 0.06 0.12 0.07 0.02 0.02 0.06 0.03 0.08 0.02 0.02 0.05 0.0460 0.08 0.03 0.03 - 0.01 - 0.1066 - 0.05 . 22 JOAN C. STEVENSON AND RENk J. DUQUESNOY ropean populations (Bodmer et al., '711. Gene frequencies for nearby Eastern and Central European populations are presented in table 3. Data is lacking for certain alleles for several of these populations because many reagents were unavailable a t the time of study. Our findings of gametic association between A1 and B8 and between A29 and B12 were not surprising since linkage disequilibrium for these antigens have been reported for most European Caucasoid populations (Bodmer et al., '72; Degos and Dausset, '74). In both Poles and Germans we found gametic association between AW30 and B13. This association has not been extensively reported for Europeans (Bodmer, et al., '72) though i t is believed that the AW30-Bl3 haplotype is common to middle Eastern populations (Degos and Dausset, '74). The gametic association A3-B7, which is common to northern European populations (Degos and Dausset, '741, was also observed in Milwaukee Germans but not in Poles. Strong linkage disequilibrium between A3 and B7 has previously been reported in Germans in Berlin (Menzel and Richter, '721, Munich (Albert et al., '721, Essen (Bertrams et al., '711, in Hannover (Gleichmann, '74). Milwaukee Poles showed significant gametic association between A25 and BIB. High A values for the A25-Bl8 haplotype have also been reported for population groups of Slavonic origin such as Ukrainians (Singal and Bhargava, '751, Yugoslavs (Kastelan e t al., '74) and Czechs (Lenhart et al., '77). In contrast, a significantly increased frequency of the A25-Bl8 haplotype was not found in Milwaukee Germans, nor has it been reported in Germans living in Berlin, Essen and Hannover. Significant gametic association between A10 and B18 has been reported for Germans in Munich (Albert et al., '721, but it is not known whether the association with B18 was for A25 or A26. The high frequencies of the A25-BI8 haplotype in Poles, Ukrainians, Yugoslavs and Czechs suggest that the spread of Slavonic culture included population movements and that the haplotype A25-Bl8 may be a slavonic marker, ACKNOWLEDGMENTS Supported by Contract HL-73-2956 and Grant AI-12507 from the National Institutes of Health. We thank the students of Pulaski High School, Milwaukee and, the Polish Women's Culture Club. LITERATURE CITED Albert, E. D., S. Schols, I. Rosenthal, €I. Baltin and J. Bertram's 1972 Study of t h e HL-A system in the Turkish and German populations. In: Histocompatibility Testing 1972. J. Dausset and J. Colombani, eds. Munksgaard, Copenhagen, pp. 147-152. Bertrams, J., I. Kuwert and U. h h m e 1971 H L A phenotype and gene frequencies in the German Ruhr area populations. European J. of Immunol., 1: 306-309. Bodmer, J. R., P. Rocques, W. F. Bodmer, J. Colombani, L. Degos, J. Dausset and A. Piazza 1972 Joint Report of t h e First Histocompatibility Workshop I Population Studies. Histocompatibility Testing 1972, pp. 621-667. Cavalli-Sforza, L. L., and W. F. Bodmer 1971 The Genetics of Human Populalions. W. €I. Freeman and Co., San Francisco. Ceppellini, R. 1967 Genetica Delle Immunoglobulin XI1 Annual Meeting of Associzione Genetica Italiana Parma AGA 12,3. Dausset, J., and J. 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