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Functional polymorphism of IL-1 alpha and its potential role in obesity in humans and mice.

ABSTRACT: Proinflammatory cytokines secreted from adipose tissue contribute to the morbidity associated with obesity. IL-1? is one of the proinflammatory cytokines; however, it has not been clarified whether IL-1? may also cause obesity. In this study, we investigated whether polymorphisms in IL-1? contribute to human obesity. A total of 260 obese subjects were genotyped for IL-1? C-889T (rs1800587) and IL-1? G+4845T (rs17561). Analyses of genotype distributions revealed that both IL-1? polymorphisms C-889T (rs1800587) and G+4845T (rs17561) were associated with an increase in body mass index in obese healthy women. In addition, the effect of rs1800587 on the transcriptional activity of IL-1? was explored in pre-adipocyte 3T3-L1 cells. Significant difference was found between the rs1800587 polymorphism in the regulatory region of the IL-1? gene and transcriptional activity. We extended these observations in vivo to a high-fat diet-induced obese mouse model and in vitro to pre-adipocyte 3T3-L1 cells. IL-1? levels were dramatically augmented in obese mice, and triglyceride was increased 12 hours after IL-1? injection. Taken together, IL-1? treatment regulated the differentiation of preadipocytes. IL-1? C-889T (rs1800587) is a functional polymorphism of IL-1? associated with obesity. IL-1? may have a critical function in the development of obesity.

SUBMITTER: Um JY

PROVIDER: S-EPMC3246492 | biostudies-literature | 2011

REPOSITORIES: biostudies-literature

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Functional polymorphism of IL-1 alpha and its potential role in obesity in humans and mice.

Um Jae-Young JY Rim Hong-Kun HK Kim Su-Jin SJ Kim Hye-Lin HL Hong Seung-Heon SH

PloS one 20111227 12

Proinflammatory cytokines secreted from adipose tissue contribute to the morbidity associated with obesity. IL-1α is one of the proinflammatory cytokines; however, it has not been clarified whether IL-1α may also cause obesity. In this study, we investigated whether polymorphisms in IL-1α contribute to human obesity. A total of 260 obese subjects were genotyped for IL-1α C-889T (rs1800587) and IL-1α G+4845T (rs17561). Analyses of genotype distributions revealed that both IL-1α polymorphisms C-88 ...[more]

PMID: 22216303

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Project description:Ankylosing spondylitis (AS) is a chronic autoimmune inflammatory disease that mainly affects the axial and sacroiliac joints. Single-nucleotide polymorphisms (SNPs) in genes encoding cytokines have been associated with AS, which can interfere with the production of these cytokines and contribute to the development of AS. In order to contribute to a better understanding of the pathology of AS, our objective was to investigate a possible association of the IL10 -1082 A>G SNP (rs1800896) with AS and to evaluate the serum levels of TNF-α, IL-10, IL-17A, and IL-17F in AS patients and controls comparing them with their respective genotypes (TNF rs1800629, IL10 rs1800896, IL17A rs2275913, and IL17F rs763780). Patients and controls were selected from the Maringá University Hospital and the Maringá Rheumatism Clinic, in Paraná State, Southern Brazil, and they were diagnosed by the ASAS Criteria. In total, 149 patients and 169 controls were genotyped for the IL10 -1082 A>G polymorphism using a polymerase chain reaction with sequence specific primers (PCR-SSP); the measurement of TNF-α serum levels was performed through the immunofluorimetric test and IL-10, IL-17A, and IL-17F using an ELISA test. There was a high frequency of the IL10 -1082 G allele in AS patients compared with controls with an odds ratio of 1.83 and 95% confidence interval of 1.32 to 2.54, and a significant difference in the genotype frequencies of the IL10 -1082 A/G+G/G between patients and healthy controls, with an odds ratio of 3.01 and 95% confidence interval of 1.75 to 5.17. In addition, increased serum levels of IL-10 were observed in AS patients: 2.38 (IQR, 0.91) pg/ml compared with controls 1.72 (IQR 0.93) pg/ml (P = 0.01). Our results also showed an association between IL17F rs763780 C/T+T/T genotypes and increased serum levels of IL-17F in patients with AS and also in controls. We can conclude that patients with the A/G and G/G genotypes for -1082 A>G (rs1800896) in the IL10 gene are three times more likely to develop AS, that the serum level of IL-10 was higher in AS patients and that the IL17F rs763780 polymorphism can affect the levels of IL-17F in the serum of patients and controls in the same way.

Dataset Information

Functional polymorphism of IL-1 alpha and its potential role in obesity in humans and mice.

Publications

Functional polymorphism of IL-1 alpha and its potential role in obesity in humans and mice.

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