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Previous issue date: 2013-03-27 / Conselho Nacional de Desenvolvimento Cient?fico e Tecnol?gico / Of all of the genes associated with the development of Diabetes mellitus type 1 (T1D), the
largest contribution comes from the genes in the Human Leukocyte Antigen (HLA) region,
mostly the class II DR e DQ genes. Specific combinations of alleles DRB1, DQA1 and DQB1
constituting haplotypes, and further, a combination of more than one haplotype, providing
multilocus genotypes are associated with susceptibility, protection and neutrality to DM1.
Thus, the aim of present study was to verified the association of polymorphisms of HLA
genes class II with susceptibility to type 1 diabetes mellitus (T1D). Ninety-two patients with
T1D and 100 individuals normoglycemics (NG) aged between 6 and 20 years were studied.
Genomic DNA was obtained from peripheral whole blood, collected in EDTA tube, using the
extraction kit Illustra Triple Prep?, GE Healthcare. For HLA typing was used DNA
LABType system by One Lambda kit applying Luminex? technology to the method of PCRSSO
typing reverse. The alleles DRB1*03:01, *04:05, *04:01, *04:02, DQA1*03:01g,
*05:01g, DQB1*02:01g, *03:02, the haplotypes DRB1*03:01-DQA1*05:01-DQB1*02:01,
DRB1*04:05-DQA1*03:01g-DQB1*03:02, DRB1*04:02-DQA1*03:01g-DQB1*03:02,
DRB1*04:01-DQA1*03:01g-DQB1*03:02 and DR3-DQ2/DR4-DQ8 genotype were
significantly associated with the chance of developing T1D. The alleles DRB1*11:01, *15:03,
*15:01, *13:01, DQA1*01:02, *04:01g, *01:03, DQB1*06:02, *03:01g, *06:03, *04:02, the
haplotypes DRB1*11:01-DQA1*05:01-DQB1*03:01, DRB1*13:01-DQA1*01:03-DQB1*06:03
and DRX-DQX/DRX-DQX genotype, formed by other than the DR3-DQ2 or DR4-DQ8
haplotypes, were significantly associated with T1D protection Despite the major racial
Brazilian, even at the regional level, these results are similar to the majority of alleles,
genotypes and haplotypes of HLA class II-related susceptibility or resistance to T1D,
extensively described in the literature for Caucasian population. Children with age at
diagnosis less than 5 years of age had significantly higher frequency of the heterozygous
genotype DR3-DQ2/DR4-DQ8 compared to children with age at diagnosis than 5 years old.
These results also demonstrate strong association of the genetic profile of the class II HLA for
this age group, possibly associated with the severity and rapid progression to the onset of
T1D. The knowledge of HLA class II genes may be useful in genetic screens that allow the
prediction of T1D / De todos os genes j? relacionados com o desenvolvimento do Diabetes mellitus tipo 1 (DM1), a
maior contribui??o vem da regi?o do genoma onde est?o localizados os genes do Ant?geno
Leucocit?rio Humano (HLA), sobretudo os genes da classe II do HLA: DR e DQ. Espec?ficas
combina??es de alelos DRB1, DQA1 e DQB1 formando hapl?tipos, e ainda, a combina??o de
mais de um hapl?tipo, formando gen?tipos multilocus s?o associados com a susceptibilidade,
neutralidade e prote??o ao DM1. Dessa forma, o objetivo do estudo foi verificar a associa??o dos
polimorfismos dos genes do complexo HLA classe II com a susceptibilidade ao DM1, em
pacientes do Rio Grande do Norte. Foram estudados 92 indiv?duos com DM1 e 100 indiv?duos
normoglic?micos (NG), com idade entre 6 e 20 anos. O DNA gen?mico foi obtido a partir do
sangue total perif?rico, coletado em tubo com EDTA, utilizando o kit de extra??o Illustra Triple
Prep?, GE Healthcare. Para a tipagem do HLA foi utilizado o sistema DNA LABType atrav?s de
kits One Lambda, que aplica a tecnologia Luminex? ao m?todo de tipagem por PCR-SSO
reverso. Os alelos DRB1*03:01, *04:05, *04:01, *04:02; DQA1*03:01g, 05:01g; DQB1*02:01g,
*03:02; os hapl?tipos DRB1*03:01-DQA1*05:01-DQB1*02:01, DRB1*04:05-DQA1*03:01g-
DQB1*03:02, DRB1*04:02-DQA1*03:01g-DQB1*03:02, DRB1*04:01-DQA1*03:01g-
DQB1*03:02 e o gen?tipo heterozigoto, DR3-DQ2/DR4-DQ8 foram significativamente
associados com a chance de desenvolvimento do DM1. J? os alelos DRB1*11:01, *15:03, *15:01,
*13:01; DQA1*01:02, *04:01g, *01:03; DQB1*06:02, *03:01g, *06:03, *04:02; os hapl?tipos
DRB1*11:01-DQA1*05:01-DQB1*03:01, DRB1*13:01-DQA1*01:03-DQB1*06:03 e o gen?tipo
DRX-DQX/DRX-DQX, formado por outros hapl?tipos que n?o DR3-DQ2 ou DR4-DQ8, foram
significativamente associados a prote??o ao DM1. Apesar da grande miscigena??o racial
brasileira, at? em n?vel regional, estes resultados s?o semelhantes a maioria dos alelos, hapl?tipos
e gen?tipos de HLA classe II relacionados ? susceptibilidade ou prote??o ao DM1,
extensivamente descritos na literatura para a popula??o caucasiana. Crian?as com idade ao
diagn?stico inferior a 5 anos de idade apresentaram significativamente maior frequ?ncia do
gen?tipo heterozigoto DR3-DQ2/DR4-DQ8, quando comparada ?s crian?as com idade ao
diagn?stico superior a 5 anos de idade. Esses resultados demonstram tamb?m forte envolvimento
do perfil gen?tico da classe II do HLA para esta faixa et?ria, que estaria relacionada
possivelmente com a gravidade e a r?pida progress?o para o in?cio do DM1. O conhecimento dos
genes HLA de classe II pode ser ?til em triagens gen?ticas que possibilitem a predi??o do DM1
| Identifer | oai:union.ndltd.org:IBICT/oai:repositorio.ufrn.br:123456789/13496 |
| Date | 27 March 2013 |
| Creators | Silva, Heglayne Pereira Vital da |
| Contributors | CPF:05410395808, http://lattes.cnpq.br/4245215108740331, Freitas, Janaina Cristiana de Oliveira Crispim, CPF:91430364491, http://lattes.cnpq.br/2644540835478572, Cunha, Nathalia de Alencar, CPF:05576360435, http://lattes.cnpq.br/5103227378217521, Rezende, Adriana Augusto de |
| Publisher | Universidade Federal do Rio Grande do Norte, Programa de P?s-Gradua??o em Ci?ncias Farmac?uticas, UFRN, BR, Bioan?lises e Medicamentos |
| Source Sets | IBICT Brazilian ETDs |
| Language | Portuguese |
| Detected Language | English |
| Type | info:eu-repo/semantics/publishedVersion, info:eu-repo/semantics/masterThesis |
| Format | application/pdf |
| Source | reponame:Repositório Institucional da UFRN, instname:Universidade Federal do Rio Grande do Norte, instacron:UFRN |
| Rights | info:eu-repo/semantics/openAccess |
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