Feasibility of genetic and immunological prediction of type I diabetes in a population-based birth cohort.
OBJECTIVE
Population-wide genetic screening of susceptibility to multifactorial diseases will become relevant as knowledge of the pathogenesis of these diseases increases and preventive interventions are identified.


METHODS
Feasibility and acceptance of neonatal genetic screening for Type I (insulin-dependent) diabetes mellitus susceptibility and adherence of the at-risk children to frequent autoantibody follow-up were studied. Screening was offered to all families. The infants with HLA-DQB1 genotypes *02/*0302 and *0302/x (x not equal to *02, *0301, *0602) were invited to autoantibody follow-up. The children who developed signs of beta-cell autoimmunity were invited to a separate prevention trial.


RESULTS
The parents of 31,526 babies born between November 1994 and April 1999 (94.4% of those eligible) agreed to genetic screening. We found that 4651 infants (14.8%) had increased genetic risk (2.5 to 15 times that of the general population) for Type I (insulin-dependent) diabetes mellitus, and 80% of them joined the autoantibody surveillance. At the age of 1, 2, 3 and 4 years, 74, 69, 68 and 76% of the at-risk children, respectively, attended the follow-up. A total of 17 of the 22 children (77%) who were born during the study period and have developed diabetes carry the risk genotypes we currently use for screening.


CONCLUSIONS
Population-based screening of genetic susceptibility for Type I diabetes, linked with a possibility to participate later in a prevention trial, is highly accepted in Finland and identifies about 75% of those developing diabetes at an early age. Families adhere well to the frequent measurement of signs of beta-cell autoimmunity in the children at-risk.
Kupila
A
A
Dept. of Paediatrics, Univ. of Turku, Kiinamyllynkatu 4-8, FIN-20520 Turku, Finland.
Muona
P
P
Simell
T
T
Arvilommi
P
P
Savolainen
H
H
Hämäläinen
A M
AM
Korhonen
S
S
Kimpimäki
T
T
Sjöroos
M
M
Ilonen
J
J
Knip
M
M
Simell
O
O
D000483:Alleles; D001323:Autoantibodies / Q000097:blood; D015331:Cohort Studies; D003922:Diabetes Mellitus, Type 1 / Q000453:epidemiology* / Q000235:genetics* / Q000276:immunology; D005240:Feasibility Studies; D005260:Female; D005387:Finland / Q000453:epidemiology; D005500:Follow-Up Studies; D005820:Genetic Testing; D005838:Genotype; D006683:HLA-DQ Antigens / Q000235:genetics*; D059866:HLA-DQ beta-Chains; D006801:Humans; D015994:Incidence; D007231:Infant, Newborn; D007515:Islets of Langerhans / Q000276:immunology; D008137:Longitudinal Studies; D008297:Male; D011237:Predictive Value of Tests; D018570:Risk Assessment; D012307:Risk Factors; D013997:Time Factors
D001323:Autoantibodies; D006683:HLA-DQ Antigens; D059866:HLA-DQ beta-Chains; C069051:HLA-DQB1 antigen