>Year 2003, Issue 3
Hermosillo-Bañuelos RM, Ramos C, Perea FJ, Rivas F, Casas-Castañeda M, Camacho AL, Sánchez YJ, Ibarra B
Analysis of HLA DQA1 and DQB1 alleles and glycated hemoglobin in healthy Mexican mestizo individuals from families with type 1 diabetes mellitus
Rev Biomed 2003; 14 (3)
PDF: 36.51 Kb.
Introduction. Variations in hemoglobin (HbA1) levels in healthy individuals are attributable to complex individual biological differences. Specific HLA DQ genes are known to predispose subjects to the development of type 1 diabetes mellitus (DM1).
Material and methods. HLA DQA1 and DQB1 genes and HbA1 heritability were investigated in healthy individuals from DM1 and non-DM1 Mexican families. HbA1 levels were determined by ionexchange chromatography and HLA class II alleles were typed by PCR, in 77 healthy persons from 18 families with at least one member suffering from DM1 (DM1R group) and in 96 healthy individuals from 18 families with no known history of DM, who constituted the control group.
Results. There were no significant inter-group differences in HbA1 levels. Mean HbA1 levels were correlated between parents and offspring, and the heritability estimate was 53% based on a regression model. DQA1 and DQB1 typing revealed inter-group differences, with an increase in the susceptibility allele, DQB1 *0201, in the DM1R group relative to the control group (17.24% vs 3.23%, respectively; p ‹ 0.05), as expected. HbA1 levels did not correlate with HLA DQA1 or DQB1 polymorphisms.
Discussion. The present data suggest that 53% of HbA1 variability is explicable by genetic factors, which do not depend on DQA1 or DQB1 polymorphisms.
||Glycated Hb, type 1 diabetes mellitus, protection alleles, DQA1 genotype, DQB1 genotype.
Bunn HF. Nonenzymatic glycosylation of protein: relevance to diabetes. Am J Med 1981; 70: 325–33.
Kilpatrick ES. Glycated haemoglobin in the year 2000. J Clin Pathol 2000; 53: 335–9.
Kilpatrick ES, Maylor PW, Keevil BG. Biological variation of glycated hemoglobin: implications for diabetes screening and monitoring. Diabetes Care 1998; 21: 261–4.
Modan M, Meytes D, Rozeman P, Yosef SB, Sehayek E, Yosef NB, et al. Significance of hgh HbA1 levels in normal glucose tolerance. Diabetes Care 1988; 11: 422–8.
Simon D, Senan C, Garnier P, Saint-Paul M, Papoz L. Epidemiological features of glycated haemoglobin A1c distribution in a healthy population. Diabetologia 1989; 32: 2305–8.
Snieder H, Sawtell PA, Ross L, Walker J, Spector TD, Leslie, Graham R D. HbA1c levels are genetically determined even in type 1 diabetes: evidence from healthy and diabetic twins. Diabetes 2001; 50: 2858–63.
Pugliese A. Unraveling the genetics of insulin-dependent type 1A diabetes: the search must go on. Diabetes Rev 1999; 7: 39–54.
Thorsby E. HLA associated diseases. Hum Immunol 1997; 53: 1–11.
Fugger L, Tisch R, Libau R, Van Endert P, McDevitt HO. The role of human major histocompatibility complex (HLA) genes in disease. In: Scriver CR, Beaudet AL, Sly WS, Valle D, editors. The metabolic and molecular bases of inherited disease. New York: McGraw-Hill; 2001. p. 311–41.
Todd JA, Bell JI, McDevitt HO. HLA-DQ-beta gene contributes to susceptibility and resistance to insulindependent diabetes mellitus. Nature 1987; 329: 599–604.
She J-X. Susceptibility to type I diabetes. HLA-DQ and DR revisited. Immunol Today 1996; 7: 323–9.
Dorman JS, LaPorte RE, Stone RA, Trucco M. Worldwide differences in the incidence of type 1 diabetes are associated with amino acid variation at position 57 of the HLA-DQb chain. Proc Natl Acad Sci USA 1990; 87: 7370–4.
Miller SA, Dykes DD, Polesky HF. A simple salting-out procedure for extracting DNA from human nucleated cells. Nucleic Acids Res 1988; 16: 1215–6.
Sambrook J, Fritsch EF, Maniatis T. Molecular Cloning: A Laboratory Manual. New York: Cold Spring Harbor; 1989.
Kimura A, Sasazuki T. 11th International Histocompatibility Workshop reference protocol for the HLA DNA-typing technique, 1992. In: HLA. Proceedings of the 11th International Histocompatibility Workshop and Conference. Oxford University Press; 1992. p. 662–5.
Bignon JD, Fernández-Viña M. (1997), PCR–SSO protocol for the HLA DNA-typing. In: HLA 1996. Charron D (Ed), HLA, 24 Kimura A, Sasazuki T, 11th International Histocompatibility Workshop reference protocol for the HLA DNA-typing technique. In: HLA. Proceedings of 11th International Histocompatibility Workshop and Conference. Oxford University Press ;1992. p. 237–40.
Zetterquist H, Olerup O. Identification of the HLA DRB1*04, DRB1*07 and RB1*09 alleles by PCR amplification with sequence-specific primers (PCR–SSP) in two hours. Hum Immunol 1992; 34: 64–74.
Olerup O, Aldener A, Fogdell A. HLA-DQB1 and HLADQA1 typing by PCR amplification with sequence-specific primers (PCR–SSP) in two hours. Tissue Antigens 1993; 41: 119–34.
Falconer D. Introduction to Quantitative Genetics. Essex: Longman Scientific & Technical; 1989. p. 167.
Leslie, Graham RD, Schneider H, Sawtell PA, Ross LJ, Walker J. The level of HbA1c is genetically determined. Diabetes 2000; 49 (Suppl 1): A75.
Peters A, Davison L, Mayer B, Schriger DL, Hasselblad DL. A clinical approach to the diagnosis of diabetes mellitus: An analysis using glycosylated hemoglobin levels. Obstet Gynecol Surv 1997; 52: 400–2.
Gorodezky C, Olivo A, Debaz H, Rodríguez L, Altamirano N, Robles C. Los mecanismos moleculares de susceptibilidad y protección dependientes del MHC en la diabetes tipo 1 en mexicanos. 1995. Gac Med Mex 131: 395–403.
Gorodezky C, Olivo A, Alaez C, Vázquez MN, de la Rosa G, Debaz H, et al. High-and low-risk molecular sequences in autoimmune diseases. An analysis of type 1 diabetes in Latin America. Gac Med Mex 1997; 133 (Suppl 1): 125–32.
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