One of the most significant epidemiologic findings regarding IDDM is that there is more than a 30-fold difference in the incidence of disease across populations, where the rates are highest in Finland and lowest in the oriental populations, such as Korea and Japan. Although the factors associated with the global patterns of IDDM incidence are unknown, it is likely that variations in the prevalence of IDDM susceptibility gene(s) are a major determinant. We have recently confirmed that the presence of an amino acid, other than aspartate, in position 57 (non-Asp-57) of the HLA-DQ beta chain is highly associated with IDDM susceptibility, such that the estimated relative risk of developing the disease was 107 for non-Asp-57 homozygotes. Although this genetic marker is strongly related to the development of IDDM among caucasians, its prevalence or relationship to IDDM in other populations or racial groups is not known. Therefore, the proposed investigation will employ a population-based epidemiologic model to determine the contribution of a specific risk factor (i.e., non-Asp-57 homozygosity) to the incidence of IDDM. The populations selected for the study represent areas of high, medium and low IDDM incidence, with caucasians, blacks and orientals. The following specific aims, formulated as null hypotheses, will therefore be tested: 1.) the prevalence of the DNA polymorphisms of the DQ beta chain gene, which are associated with IDDM susceptibility, do not vary across populations or ethnic groups, 2.) the strength of the associations between these molecular markers and IDDM does not differ across populations, 3.) the geographic and racial variations in the incidence of IDDM across the world are unrelated to differences in the prevalence of the genetic markers of IDDM susceptibility.

Agency
National Institute of Health (NIH)
Institute
National Institute of Diabetes and Digestive and Kidney Diseases (NIDDK)
Type
Research Project (R01)
Project #
3R01DK042316-04S1
Application #
2142234
Study Section
Epidemiology and Disease Control Subcommittee 2 (EDC)
Project Start
1990-09-15
Project End
1996-08-31
Budget Start
1995-09-01
Budget End
1996-08-31
Support Year
4
Fiscal Year
1995
Total Cost
Indirect Cost
Name
University of Pittsburgh
Department
Public Health & Prev Medicine
Type
Schools of Public Health
DUNS #
053785812
City
Pittsburgh
State
PA
Country
United States
Zip Code
15213
McLean, Leon P; Cross, Raymond K; Shea-Donohue, Terez (2013) Combined blockade of IL-17A and IL-17F may prevent the development of experimental colitis. Immunotherapy 5:923-5
Cardwell, Chris R; Stene, Lars C; Ludvigsson, Johnny et al. (2012) Breast-feeding and childhood-onset type 1 diabetes: a pooled analysis of individual participant data from 43 observational studies. Diabetes Care 35:2215-25
Strotmeyer, Elsa S; Yang, Ze; LaPorte, Ronald E et al. (2004) Infant diet and type 1 diabetes in China. Diabetes Res Clin Pract 65:283-92
Dorman, J S; Bunker, C H (2000) HLA-DQ locus of the human leukocyte antigen complex and type 1 diabetes mellitus: a HuGE review. Epidemiol Rev 22:218-27
Dorman, J S (2000) Molecular epidemiology: the impact of molecular biology in epidemiology research. Rev Med Chil 128:1261-8
Dorman, J (1997) Molecular epidemiology of insulin-dependent diabetes mellitus: WHO DiaMond Project. WHO DiaMond Molecular Epidemiology Sub-Project Group. Gac Med Mex 133 Suppl 1:151-4
Dorman, J; Siulc, E S (1997) Postgraduate programs in molecular epidemiology. Gac Med Mex 133 Suppl 1:83-6
Dorman, J S; McCarthy, B; McCanlies, E et al. (1996) Molecular IDDM epidemiology: international studies. WHO DiaMond Molecular Epidemiology Sub-Project Group. Diabetes Res Clin Pract 34 Suppl:S107-16
Lampasona, V; Ferrari, M; Bonifacio, E et al. (1995) HLA-DQ screening for risk assessment of insulin dependent diabetes in northern Italy. Acta Diabetol 32:137-42
Kocova, M; Siegel, S F; Wenger, S L et al. (1995) Detection of Y chromosome sequences in a 45,X/46,XXq--patient by Southern blot analysis of PCR-amplified DNA and fluorescent in situ hybridization (FISH). Am J Med Genet 55:483-8

Showing the most recent 10 out of 12 publications