Abstract
HLA-DQα and HLA-DXα gene polymorphisms were analyzed by Southern blot techniques in 78 Caucasoid insulin-dependent diabetes mellitus (IDDM) subjects and 55 control subjects. Five restriction fragment length polymorphisms of the HLA-DQ α gene correlated with HLA-DR typing. Two allelic DX α-related gene fragments, of 2.1 kb (U) and 1.9 kb (L) in size were identified. Genotype frequencies in the IDDM group for UU, UL, and LL were 54%, 38.5%, and 7.5%, respectively, whereas the corresponding frequencies in the control group were 24%,40%, and 36% (P < 0.00005 for differences in genotype frequencies).
The U allele was associated particularly with IDDM patients who were DR3, with healthy controls who were DR3, as well as with IDDM patients who were not DR3. Thus, if this DX α U allele is not the DR3-associated IDDM susceptibility gene, it is the closest marker hitherto studied.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Auffray, C. and Strominger, J. L.: Molecular genetics of the human major histocompatibility complex. Adv. Hum. Genet., in press, 1985
Auffray, C., Lillie, J. W., Arnot, D., Grossberger, D., Kappes, D., and Strominger, J. L.: Isotypic and allotypic variation of human class Il histocompatibility antigen α-chain genes. Nature 308: 327333, 1984
Cohen-Haguenauer, O., Robbins, E., Massart, C., Bussom, M., Deschamps, I., Hors, J., Lalouel, J., Dausset, J., and Cohen, D. A systematic study of the HLA class II β DNA restriction fragments in insulin dependent diabetes mellitus. Proc. Natl. Acad. Sci. U.S.A. 82: 3335–3339, 1985
Cudworth, A. G. and Festenstein H.: HLA heterogeneity in diabetes mellitus. Br. Med. Bull. 34: 285–290, 1978
Festenstein, H., Adam, F., Burke, J., Other, R. T. D., Sachs, J. A., and Wolf, E.: The distribution of HL-A antigens in expatriates from East Bengal living in London, In J. Dausset (ed.): Histocompatibility Testing 1972, pp. 175–178, Munksgaard, Copenhagen, 1972
Hitman, G. A., Tarn, A. C., Winter, R. M., Drummond, V., Williams, L. G., Jowett, N. I., Bottazzo, G. F., and Galton, D. J.: Type 1 (insulin-dependent) diabetes and a highly variable locus close to the insulin gene on chromosome II. Diabetologia 28: 218–222, 1985
Hui, K. M., Groves, A. V., Jaraquemada, D., Groseveld, F., Awad, J., Navarrette, C., Trowsdale, J., Murray, E., and Festenstein, H.: DNA restriction fragment length polymorphism of the human class 11 genes as analyzed by Southern blotting technique. In E. Albert, M. P. Baur, and W. R. Mayr (eds.): Histocompatibility Testing 1984, pp. 590–594, Springer-Verlag, Berlin, 1984
Kunkel, L. M., Smith, K. D., Boyer, S. H., Borgoanker, D. S., Wachtel, S. S., Miller, O. J., Breg, W. R., Jones, H. W., Jr., and Rary, J. M.: Analysis of human Y chromosome specified reiterated DNA in chromosome variants. Proc. Natl. Acad. Sci. U.S.A. 74: 1245–1249, 1977
McCluskey, J., McCann, V. J., Kay, P. H., Zilko, P. J., Christiansen, F. T., O'Neill, G. J., and Dawkins, R. L.: HLA and complement allotypes in type 2 (insulin-dependent) diabetes. Diabetologia 24: 162–165, 1983
Nerup, J., Cathelineau, C., Seignalet, J., and Thomsen, M.: In J. Dausset and A. Svejgaard (eds.): HLA and Disease, pp. 149–167, Munksgaard, Copenhagen, 1970
Okoye, R. C., Williams, E., Alonso, A., Doyle, P., Awad, J., Nawavette, C., Jaraquemada, J., Ollier, W. E., and Festenstein, H.: HLA polymorphisms in Nigerians. Tissue Antigens 25: 142–155, 1985
Owerbach, D., Lernmark, A., Platz, P., Ryder, L. P., Rask, L., Peterson, P. A., and Ludvigsson J.: HLA-D region β chain DNA endonuclease fragments differ between HLA-DR identical healthy and insulin-dependent diabetic individuals. Nature 303: 815–817, 1983
Raum, D., Awdeh, Z., Yams, E. J., Alper, C. A., and Gabbay, K. H.: Extended major histocompatibility complex haplotypes in type 1 diabetes mellitus. J. Clin. Invest. 74: 449–454, 1984
Rich, S., O'Neill, G., Dalmasso, A. P., Nerl, C., and Barbosa, J.: Complement and HLA: Further definition of high risk haplotypes in insulin dependent diabetes. Diabetes 34: 504–509, 1985
Sachs, J. A., Cudworth, A. G., Jaraquemada, D., Gorsuch, A. N., and Festenstein, H.: Type 1 diabetes and the HLA-D locus. Diabetologia 418: 41–43, 1980
Southern, E. M.: Detection of specified sequences among DNA fragments separated by gel electrophoresis. J. Mol. Biol. 98: 503517, 1975
Spielman, R. S., Lee, J., Bodmer, W. F., Bodmer, J. G., and Trowsdale, J.: Six HLA-D region a chain genes on human chromosome 6: Polymorphisms and associations of DCα-related sequences with DR types. Proc. Natl. Acad. Sci. U.S.A. 81: 3461–3465, 1984
Svejgaard, A., Platz, P., and Ryder, L. P.: Joint report: Insulin dependent diabetes mellitus. In P. I. Terasaki (ed.): Histocompatibility Testing 1980, pp. 638–654, UCLA Tissue Typing Laboratory, Los Angeles, 1980
van Rood, J. J., van Leeuwen, A., and Ploem, J. S.: Simultaneous detection of two cell populations by two color fluorescence and application on the recognition of β cell determinants. Nature 262: 795–797, 1976
Wolf E., Spencer, K. M., and Cudworth, A. G.: The genetic susceptibility to type 1 (insulin dependent) diabetes: Analysis of the HLADR association. Diabetologia 24: 224–230, 1984
Author information
Authors and Affiliations
Rights and permissions
About this article
Cite this article
Hitman, G.A., Sachs, J., Cassell, P. et al. A DR3-related DXα gene polymorphism strongly associates with insulin-dependent diabetes mellitus. Immunogenetics 23, 47–51 (1986). https://doi.org/10.1007/BF00376521
Received:
Revised:
Issue Date:
DOI: https://doi.org/10.1007/BF00376521