Affiliations: Escola Paulista de Medicina/UNIFESP, Sao Paulo, SP,
Brazil | Fleury Institute, Sao Paulo, SP, Brazil | PerkinElmer Life and Analytical Sciences, Turku,
Finland | JDRF Centre for Prevention of Type 1 Diabetes in
Finland and Department of Virology, University of Turku, Turku, Finland
Note: [] Corresponding author: Jorma Ilonen, University of
Turku/Medicity, Tykistökatu 6A, Turku, Finland. Tel.: +358 2 3337028; Fax:
+358 2 3337000; E-mail: [email protected]
Abstract: The study aimed to further characterise HLA encoded risk factors of
type 1 diabetes (T1D) in Brazilian population and test the capability of a low
resolution full-house DR-DQ typing method to find subjects at diabetes risk.
Insulin and CTLA-4 gene polymorphisms were also analysed. The method is based
on an initial DQB1 typing supplemented by DQA1 and DR4 subtyping when
informative. Increased frequencies of both (DR3)-DQA1*05-DQB1*02 and
DRB1*04-DQA1*03-DQB1*0302 haplotypes were detected among patients. DRB1*0401,
*0402, *0404 and *0405 alleles were all common in DQB1*0302 haplotypes and
associated with T1D. (DRB1*11/12/1303)-DQA1*05-DQB1*0301,
(DRB1*01/10)-DQB1*0501, (DRB1*15)-DQB1*0602 and (DRB1*1301)-*0603 haplotypes
were significantly decreased among patients. Genotypes with two risk haplotypes
or a combination of a susceptibility associated and a neutral haplotype were
found in 78 of 126 (61.9%) T1D patients compared to 8 of 75 (10.7%) control
subjects (P < 0.0001). Insulin gene −2221 C/T polymorphism was also
associated with diabetes risk: CC genotype was found among 83.1% of patients
compared to 69.3% of healthy controls (P=0.0369, OR 1.98) but CTLA-4 gene
+49 A/G polymorphism did not significantly differ between patients and
controls. Despite the diversity of the Brazilian population the screening
sensitivity and specificity of the used method for T1D risk was similar to that
obtained in Europe.
