Type 1 diabetes susceptibility determined by HLA alleles and CTLA-4 and insulin genes polymorphisms in Brazilians.
BACKGROUND
Type 1A diabetes mellitus (T1ADM) is a multifactorial disease in which genetic and environmental aspects are important to its development. The association of genetic variations with disease has been demonstrated in several studies; however, the role of some gene loci has not yet been fully elucidated.


OBJECTIVE
To compare the frequency of HLA alleles and polymorphism in CTLA-4 and insulin genes in Brazilians with T1ADM and individuals without the disease, as well as to identify genetic markers that are able to discriminate between diabetic and non-diabetic individuals.


METHODS
The presence of HLA DQB1, DQA1 and DRB1 alleles, as well as the -2221 MspI polymorphism in the insulin gene and 49 A/G in the CTLA-4 gene were identified by the 'Time-resolved fluorometer' technique after hybridization with probes labeled with Eu (III) / Sm (III) and Tb (III).


RESULTS
The DQB1 *0302 and DQA1 *03 alleles were identified as predisposed to T1ADM, and the DQB1 *0301 allele presented a protective effect against the disease.The DQA1 label proved to be able to differentiate between 71.13% of the diabetic and non-diabetic individuals.This value increased to 82.47% when the DQB1 label was added. No significant difference in the frequency of polymorphisms in the insulin and CTLA-4 genes was observed between the two groups.


CONCLUSIONS
The genetic markers that best characterized and discriminated diabetic and non-diabetic individuals were the HLA DQA1 and DQB1.alleles.
Ferreira
Alessandro Clayton Souza
AC
Departamento de Biologia Geral, Instituto de Ciências Biológicas, Universidade Federal de Minas Gerais (UFMG), Belo Horizonte, MG, Brazil. alessandro@labhpardini.com.br
Gomes
Karina Braga
KB
Sampaio
Ivan Barbosa Machado
IB
Oliveira
Vanessa Cristina de
VC
Pardini
Victor Cavalcanti
VC
Godard
Ana Lucia Brunialti
AL
D000293:Adolescent; D000328:Adult; D000483:Alleles; D015703:Antigens, CD / Q000235:genetics*; D060908:CTLA-4 Antigen; D016022:Case-Control Studies; D003922:Diabetes Mellitus, Type 1 / Q000235:genetics*; D016002:Discriminant Analysis; D005787:Gene Frequency; D020022:Genetic Predisposition to Disease / Q000235:genetics; D005838:Genotype; D006681:HLA-D Antigens / Q000235:genetics*; D006801:Humans; D007328:Insulin / Q000235:genetics*; D011110:Polymorphism, Genetic / Q000235:genetics*
D015703:Antigens, CD; D060908:CTLA-4 Antigen; C556706:CTLA4 protein, human; D006681:HLA-D Antigens; D007328:Insulin