Association between toll-like receptor polymorphisms and serum levels of tumor necrosis factor-alpha and its soluble receptors in obese children.
BACKGROUND
In obesity, increased tumor necrosis factor (TNF)-alpha level is involved in the development of insulin resistance. Toll-like receptor (TLR)-4 and TLR2 are expressed in adipose tissue, and polymorphisms of these receptors may influence TNF-alpha secretion from adipocytes. In our study, TNF-alpha, soluble TNF receptor 1 (sTNFR1), and soluble TNF receptor 2 (sTNFR2) levels were determined, and any association between polymorphisms of TLR4 (D299G, T399I), TLR2 (R753Q, R677W), and cytokine levels was assessed in obese children and non-obese control subjects.


METHODS
In a cross-sectional study, 79 obese children and 42 matched non-obese control children were investigated. Cytokine levels were measured by enzyme amplified sensitivity immunoassay. TLR4 and TLR2 polymorphisms were determined using polymerase chain reaction - restriction fragment length polymorphism technique.


RESULTS
TNF-alpha and sTNFR2 levels in obese children were significantly (P<.01) higher than controls. Significant (P<.05), positive, linear correlations were observed between TNF-alpha, sTNFR2 levels, and BMI. Patients carrying the mutant alleles of TLR4 (299G and 399I) had lower TNF-alpha and sTNFR2 levels compared to patients carrying wild-type alleles (299D and 399T) (TNF-alpha 4.4+/-0.7 pg/mL vs 5.5+/-0.9 pg/mL; sTNFR2 2.9+/-1.2 ng/mL vs 4.4+/-1.1 ng/mL; P<.001). The R753Q polymorphism of TLR2 was not associated with altered cytokine levels, and the R677W polymorphism was not detected in the sample population.


CONCLUSIONS
Serum levels of TNF-alpha and its soluble receptors are elevated and associated with increasing BMI values in obese children. Serum cytokine levels, as modifying factors of insulin resistance, may be affected by TLR4 polymorphisms in obese children.
Jermendy
Agnes
A
1st Department of Paediatrics, Semmelweis University, Budapest, 1083, Hungary. jermendy@gmail.com
Korner
Anna
A
Kovacs
Margit
M
Kaszas
Edit
E
Balázsovics
Judit
J
Szocs
Albert
A
Madacsy
Laszlo
L
Cseh
Karoly
K
D000293:Adolescent; D000483:Alleles; D015992:Body Mass Index; D002648:Child; D003430:Cross-Sectional Studies; D016207:Cytokines / Q000378:metabolism; D004797:Enzyme-Linked Immunosorbent Assay / Q000379:methods; D005260:Female; D006801:Humans; D007333:Insulin Resistance / Q000235:genetics; D008297:Male; D009765:Obesity / Q000097:blood* / Q000235:genetics*; D011110:Polymorphism, Genetic; D051195:Toll-Like Receptor 2 / Q000235:genetics; D051197:Toll-Like Receptor 4 / Q000235:genetics; D051193:Toll-Like Receptors / Q000235:genetics*; D014409:Tumor Necrosis Factor-alpha / Q000097:blood* / Q000235:genetics*
D016207:Cytokines; C495342:TLR2 protein, human; C495345:TLR4 protein, human; D051195:Toll-Like Receptor 2; D051197:Toll-Like Receptor 4; D051193:Toll-Like Receptors; D014409:Tumor Necrosis Factor-alpha