Association of extended interleukin-10 promoter haplotypes with disease susceptibility and manifestations in German patients with systemic lupus erythematosus.
Lupus
; 23(4): 378-85, 2014 Apr.
Article
em En
| MEDLINE
| ID: mdl-24536045
ABSTRACT
OBJECTIVES:
Associations of interleukin-10 (IL-10) promoter single nucleotide polymorphisms (SNPs) and their haplotypes with systemic lupus erythematosus (SLE) are unclear. We extended the analysis of established proximal IL-10 promoter haplotypes to a more distal SNP with functional capacity.METHODS:
Two hundred and ten German caucasian SLE patients fulfilling the ACR criteria and 160 ethnically, age and sex matched controls were genotyped for IL-10 -2849 G > A, -1082 A > G, -819 T > C and -592 C > A. Haplotypes were reconstructed via a mathematical model, then allele and haplotype distributions were compared between patients and controls and patients with different disease manifestations.RESULTS:
We detected at -2849, -1082, -819 and -592 the four predominant haplotypes GGCC (22% in patients vs. 29% in controls), AGCC (24% vs. 21%), GACC (30% vs. 25%) and GATA (24% vs. 24%). GGCC was underrepresented in SLE patients, suggesting a protective effect (odds ratio (OR) 0.67, 95% confidence interval (CI) 0.48-0.94). AGCC was found significantly more frequently in patients with pathognomonic anti-dsDNA antibodies (26% vs. 15%; OR 1.98, 95% CI 1.04-3.75). As compared to patients with glomerulonephritis type V (WHO classification), the presumptive IL-10 high producer allele -2849 G was found significantly more often in patients with GN type III/IV (93% vs. 60%; OR 8.7, 95% CI 1.59-47.15).CONCLUSION:
Our data confirm that the complexity of the IL-10 promoter evokes the need for a meticulous analysis of its haplotypic structure in order to specify disease associations, particularly under functional aspects, thereby shedding light on the pathophysiology of SLE.Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Interleucina-10
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Predisposição Genética para Doença
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Lúpus Eritematoso Sistêmico
/
Modelos Teóricos
Tipo de estudo:
Observational_studies
/
Prognostic_studies
/
Risk_factors_studies
Limite:
Female
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Humans
/
Male
País/Região como assunto:
Europa
Idioma:
En
Revista:
Lupus
Assunto da revista:
REUMATOLOGIA
Ano de publicação:
2014
Tipo de documento:
Article
País de afiliação:
Alemanha