TNFa microsatellite polymorphism modulates the risk of type 1 diabetes in the Belgian population, independent of HLA-DQ.
Hum Immunol
; 68(8): 690-7, 2007 Aug.
Article
en En
| MEDLINE
| ID: mdl-17678725
ABSTRACT
To determine the contribution of the tumor necrosis factor alpha gene (TNFA) to the immunogenetic risk prediction of type 1 diabetes (T1D) in the Belgian population, well-characterized antibody-positive patients with type 1 diabetes (T1D), nondiabetic control subjects, and nuclear families were analyzed for HLA-DQA1-DQB1, TNFA -308 G/A promoter single nucleotide polymorphism (SNP) and TNFa microsatellite markers in both case-control and transmission studies. A total of 1,029 patients (mean age at onset, 18 years; male/female ratio, 1.2), 575 control subjects and 179 nuclear families were analyzed for the -308 SNP and 1,082 patients (mean age at onset, 17 years; and male/female ratio, 1.3), 606 control subjects, and 261 nuclear families were analyzed for the TNFa microsatellite marker. All subjects were typed initially for HLA-DQ. No primary association was detected with the -308 G/A promoter SNP. In contrast, we found evidence of a contribution of TNFa1 allele to susceptibility for T1D independently of HLA-DQ. We observed that the conserved HLA-DQ-TNFa extended haplotype, HLA-DQA1 0501-DQB1 0201-TNFa1 is a diabetogenic haplotype in the Belgian population and is independent of age at onset and gender and confers an estimated relative risk of 4.55 and an absolute risk of 1.7%. In conclusion, our observations suggest that the-308 G/A promoter SNP is not a genetic marker for T1D, but that the TNFa microsatellite may have an added value to further refine the immunogenetic risk conferred by the HLA-DQ region in the Belgian population.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Antígenos HLA-DQ
/
Factor de Necrosis Tumoral alfa
/
Repeticiones de Microsatélite
/
Polimorfismo de Nucleótido Simple
/
Diabetes Mellitus Tipo 1
Tipo de estudio:
Etiology_studies
/
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Límite:
Adolescent
/
Adult
/
Female
/
Humans
/
Male
País/Región como asunto:
Europa
Idioma:
En
Revista:
Hum Immunol
Año:
2007
Tipo del documento:
Article
País de afiliación:
Bélgica