Correlation of methylation of toll-like receptor 4 (TLR4) and interleukin-6 (IL6) promoter with insulin resistance in obese adolescents
ABSTRACT: Chronic inflammation
can lead to insulin resistance in obesity. Increased mRNA expression of
inflammatory markers such as toll-like receptor 4 (TLR4) and interleukin 6 (IL6)
were reported both in the tissue and the peripheral blood of obese adolescent
and correlated with insulin resistance. DNA methylation surrounding TSS region
is known to regulate thelevel of a gene expression. The aim of the study was to
investigate the methylation status of TLR4 and IL6 promoter in peripheral blood
of obese adolescent and its correlation to insulin resistance. This was a cross
sectional study with observational analytic approached. Fifty adolescents with
obesity from Yogyakarta Special Region, aged 15-18 years, z-score value >2
SD, no experience of any acute infections within 2 weeks and signed in informed
consent, were selected in this study. Subjects with diabetic mellitus,
incompletedata and DNA concentration of <20 µg/mL were excluded. DNA samples
were extracted from peripheral blood of the subjects. The bisulfte converted
DNA was analyzed for methylation level with direct sequencing. Correlation
analysis using Spearman test was performed with signifcance value was set at
p<0.05. No methylation in TLR4 promoter was detected in all subjects. The
methylation level of IL6 was transformed to categorical variable. Four (8%)
subjects with insulin resistance and 2 (4%) without insulin resistancehad
methylation on a CpG site. Methylation of IL6 was not statisticaly different
between insulin resistance and non-resistance adolescent (p=0.635). The
signifcant correlationwas not found between methylation level in IL6 promoter
with insulin resistance (HOMAIR) (r=0.051). Cell specifc of methylation
mechanism, characteristic of subjects and types of samples were suspected
causing those results. In conclusion, no correlation between methylation levels
of TLR4 promoter and IL6 with insulin resistance in obese adolescent was
observed in this study.
Author: Ratih Feraritra Danu
Atmaja, Dian Caturini Sulistyonigrum, Emy Huriyati, Ahmad Hamim Sadewa, Rina
Susilowati
Journal Code: jpkedokterangg160179
