Temporal changes in the frequencies of HLA genotypes in patients with Type 1 diabetes—indication of an increased environmental pressure?
Tóm tắt
The incidence of Type 1 diabetes has increased 2.5 times during the time period from 1966 to 2000 in Finland—a general trend seen in almost all developed countries that can only be explained by environmental factors. The aim of this study was to test the possible effect of a changing environment on distribution of genotypes associated with disease susceptibility. HLA DRB1-DQA1-DQB1 genes and two diabetes-associated polymorphisms at IDDM2 and IDDM12 were analyzed. The frequencies of genotypes were compared between cases diagnosed with childhood-onset Type 1 diabetes during the period of 1939–1965 (n=367) and those diagnosed between 1990 and 2001 (n=736). Chi-square statistics or the Fisher's Exact test were used for the comparison of frequencies of analyzed haplotypes and genotypes in the two groups. The frequencies of (DR3)-DQA1*05-DQB1*02 and (DR4)-DQB1*0302 risk haplotypes and the high risk (DR3)-DQA1*05-DQB1*02/DRB1*0401-DQB1*0302 genotype were higher while proportion of patients carrying protective haplotypes—(DR15)-DQB1*0602 and (DR1301)-DQB1*0603—or protective genotypes was lower in patients diagnosed before 1965 as compared to those who developed disease after 1990. No temporal variation was found in the frequencies of genotypes at IDDM2 and IDDM12. Our data suggest that the need for genetic susceptibility to develop Type 1 diabetes has decreased over time due to an increasing environmental pressure and this results in a higher disease progression rate especially in subjects with protective HLA genotypes.
Tài liệu tham khảo
Piazza A, Menozzi P, Cavalli-Sforza LL (1980) The HLA-A,B gene frequencies in the world: migration or selection? Hum Immunol 1:297–304
Hill AV, Allsopp CE, Kwiatkowski D et al. (1991) Common west African HLA antigens are associated with protection from severe malaria. Nature 352:595–600
Dunstan SJ, Stephens HA, Blackwell JM et al. (2001) Genes of the class II and class III major histocompatibility complex are associated with typhoid fever in Vietnam. J Infect Dis 183:261–268
Thursz MR, Thomas HC, Greenwood BM, Hill AV (1997) Heterozygote advantage for HLA class-II type in hepatitis B virus infection. Nat Genet 17:11–12
Karvonen M, Viik-Kajander M, Moltchanova E, Libman I, LaPorte R, Tuomilehto J (2000) Incidence of childhood type 1 diabetes worldwide. Diabetes Mondiale (DiaMond) Project Group. Diabetes Care 23:1516–1526
Tuomilehto J, Rewers M, Reunanen A et al. (1991) Increasing trend in Type I (insulin-dependent) diabetes mellitus in childhood in Finland. Analysis of age, calendar time and birth cohort effects during 1965 to 1984. Diabetologia 34:282–287
Mäenpää A, Koskimies S, Scheinin T et al. (1991) Frequencies of HLA-DR3, -DR4, -B8 and -Bw62 in diabetic children diagnosed between 1960 and 1990. Diabetes Res 16:159–163
Kontiainen S, Scheinin T, Schlenzka A, Mäenpää J, Groop L, Koskimies S (1988) Differences in HLA types in children with insulin-dependent diabetes diagnosed in 1960s, 1970s, and 1980s. Lancet ii:219
Nejentsev S, Sjöroos M, Soukka T et al. (1999) Population-based genetic screening for the estimation of Type 1 diabetes mellitus risk in Finland: selective genotyping of markers in the HLA-DQB1, HLA-DQA1 and HLA-DRB1 loci. Diabet Med 16:985–992
Laaksonen M, Pastinen T, Sjöroos M et al. (2002) HLA class II associated risk and protection against multiple sclerosis—a Finnish family study. J Neuroimmunol 122:140–145
Chowdhury TA, Dyer PH, Mijovic CH, Dunger DB, Barnett AH, Bain SC (1999) Human leucocyte antigen and insulin gene regions and nephropathy in type I diabetes. Diabetologia 42:1017–1020
Ronningen KS, Bangstad HJ, Undlien DE, Thorsby E (1993) Influence of genetic factors (HLA class II genes, insulin-gene region polymorphisms) and metabolic control on the development of diabetic nephropathy. Diabetes Res 23:31–40
Caillat-Zucman S, Garchon HJ, Timsit J et al. (1992) Age-dependent HLA genetic heterogeneity of type 1 insulin-dependent diabetes mellitus. J Clin Invest 90:2242–2250
Komulainen J, Kulmala P, Savola K et al. (1999) Clinical, autoimmune, and genetic characteristics of very young children with type 1 diabetes. Childhood Diabetes in Finland (DiMe) Study Group. Diabetes Care 22:1950–1955
Hermann R, Mijovic CH, Rayner M et al. (2001) HLA alleles and IDDM in children in Hungary: a comparison with Finland. Hum Immunol 62:391–398
Nejentsev S, Koskinen S, Sjöroos M et al. (1998) Distribution of insulin-dependent diabetes mellitus (IDDM)-related HLA alleles correlates with the difference in IDDM incidence in four populations of the Eastern Baltic region. Tissue Antigens 52:473–477
Noble JA, Valdes AM, Cook M, Klitz W, Thomson G, Erlich HA (1996) The role of HLA class II genes in insulin-dependent diabetes mellitus: molecular analysis of 180 Caucasian, multiplex families. Am J Hum Genet 59:1134–1148
Viskari HR, Koskela P, Lönnrot M et al. (2000) Can enterovirus infections explain the increasing incidence of type 1 diabetes? Diabetes Care 23:414–416
Bach JF (2002) The effect of infections on susceptibility to autoimmune and allergic diseases. N Engl J Med 347:911–920
Vaarala O (2002) The gut immune system and type 1 diabetes. Ann NY Acad Sci 958:39–46
Lucassen AM, Julier C, Beressi JP et al. (1993) Susceptibility to insulin dependent diabetes mellitus maps to a 4.1 kb segment of DNA spanning the insulin gene and associated VNTR. Nat Genet 4:305–310
Bell GI, Horita S, Karam JH (1984) A polymorphic locus near the human insulin gene is associated with insulin-dependent diabetes mellitus. Diabetes 33:176–183
Nistico L, Buzzetti R, Pritchard LE et al. (1996) The CTLA-4 gene region of chromosome 2q33 is linked to, and associated with, type 1 diabetes. Belgian Diabetes Registry. Hum Mol Genet 5:1075–1080
Morahan G, Huang D, Tait BD, Colman PG, Harrison LC (1996) Markers on distal chromosome 2q linked to insulin-dependent diabetes mellitus. Science 272:1808–1810
Marron MP, Raffel LJ, Garchon HJ et al. (1997) Insulin-dependent diabetes mellitus (IDDM) is associated with CTLA4 polymorphisms in multiple ethnic groups. Hum Mol Genet 6:1275–1282