the relation of interleukin 6 gene-190 t/c polymorphisms with anthropometric and biochemical...
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The Relation of Interleukin 6 Gene-190 T/C Polymorphisms with Anthropometric and Biochemical
Characteristics in a group of Obese Children
Authors: Mărginean Maria Oana, Tripon Florin
Coordinators: Bănescu Claudia, Pitea Ana Maria
Introduction
• Genetic variability of the IL-6-190 gene in humans-allele T or C
• Asociated with other hereditary diseases– Including nutritional disorders
• malnutrition• obesity
Introduction
• Obesity– represents a problem with great importance and certain
actuality in the field of pediatric pathology because of its increased incidence in children and its complications (cardiovascular, metabolic, renal)
– Excessive or abnormal accumulation of fat in the adipose tissue
– Recent data suggests that obesity
• may have an inflammatory etiology
• asociates a low-degree proinflammatory status
Background
• Pathogenesis
– genetic factors
– environmental factors
• diet – excesive intake
• decrease in physical activity
– psycho-emotional factors
– stress
Introduction
• the adipocyte:– secretes hormones, growth factors, cytokines
(proinflammatory)
– receptors for hormones, cathecolamines, prostaglandines
– influences the energetic metabolism
Introduction
• the adipocyte stocks cytokines (IL6, TNFα)
• The cytokine level (IL) was bigger in the supraponderal and obese children, in comparison with the normoponderal group
– positively corelated with the antropometric indexes
– and with different complications
IL-6• IL-6 - an inflammatory cytokine involved in the regulation of energy
balance
• IL-6 regulates the acute phase response and inflammation, which influence the function of adipose tissue, the levels of IL6 being increased in obese patients and with cardiovascular diseases
• IL-6 deficit - associated with obesity, hypofunction of T cells, and neuroendocrine/ metabolic dysfunction
• the C allele has been associated with a risk of high blood pressure and of coronary disease.
• studies reported a positive correlation between TNF-ɑ, IL-6, the level of leptin, the mass of adipose tissue and BMI
• possible marker of obesity complications
the IL-6 gene 190 T/C polymorphism influences the producing and plasma-level of this cytokine
Objective
• the study of clinical and genetic factors in children with obesity
• I examined if the obese patients are different concerning the IL-6 – 190 genotypes
• and also the correlation of this genotype with
– anthropometric and
– biochemical parameters
Material and methods• 182 children divided in 2 comparable age and
gender groups– admitted in Pediatrics Clinic I
– in the period October 2012 – March 2014
• 86 with obesity • 96 with normal weight/ control group
• the following were evaluated:– anthropometric parameters
– biochemical metabolism parameters
– cytokine levels
Material and methods• anthropometric parameters
• BMI, body mass index
• medium upper-arm circumference / MUAC
• Tricipital skinfold/ TSF
– biochemical metabolism parameters• proteins, lipidic prophile, albumins
– IL-6 190 T/C polymorphism analysis (using specific primers).
Material and methods• Including criteria in the study
– control group – healthy pediatrics patients– obese children
• children and adolescents with obesity• children with increased weight, BMI, MUAC and TSF
• excluding criteria: – Children and adolescents with genetic diseases– Metabolic disorders that could influence the weight– Other chronic diseases that could influence the nutritional
status
• Statistical calculation
– For the entire statistical calculation
• Graph Pad 3.6 Software, San Diego, California, United Stated of Smerica
– For the evaluation of the normality of continuous variables (for example IMC, MUAC, TST, etc)
• I applied the t-Student test
• Expressing the anthropometric parameters measured as standard deviations (Z score) and calculation of some correlative indexes
Material and methods
Results
• the medium age of the children included in the study
– 9.67 ± 3.52 years in control group
– 9.21± 2.11 years in obese group
• without significant statistical difference between the two groups
Results – anthropometry
ParameterControlN=86
ObeseN=96
p
BMI z (median-range) -0.04 (-1,54-1.9) 2.81 (2-7.18) 0.0001
MUAC z (median-
range)-0.26 (-5.5-7.8) 4.8 (-1.3-13.9) 0.0001
TST z (median-range) -0.9 (-5.9-9.41) 2.91 (-1.3-8.65) 0.0001
Proteins obese vs. control
T chol obese vs. control
Results - biochemistry
Parameter
ControlN=86
ObeseN=96
p
Glicemya 84,7 ± 3,43 99.67 ± 2,13 0,08
Proteins 7.2 ± 0.55 8.1± 0.53 0,04
Total Chol
146 ± 23.48
162.17 ± 14.64 <0.05
Glicemya obese vs. control
VariablesControl group
(n = 86)
Obese
(n = 96)p value
IL-6 190
no (%)
CC 30 (34.88) 14 (14.58) 0.0001
CT 37 (43.02) 71 (73.95) 0.0001
TT 19 (22.09) 11 (11.45) 0.08
Results - polymorphisms
• The CT genotype was observed to appear more frequently in the obese group (73.95%) than in the control group (p=0.0001)
• CC homozygotes, as well as the T allele, predominated in the control group
Anthropometric and
paraclinical parameters
CC
CT TT
control obese p value control obese p value control obese p value
MUAC# SD median (range)
-0.36(-5.3-9.1)
4.4(-1.3-6.2)
0.0001-0.25
(-2.93-9.1)4.6
(-1.12-10.1)
0.0001-0.25
(-1.9-7.5)
3.6(-1.06-
7.8)
0.0001
TST# SDmedian (range)
-0.87(-5.9-3.9)
2.13(-1.37-3.4)
0.0001 -0.06(-2.9-6.9)
3.2(0.2-8.2)
0.0001 -0.25(-3.9-9.1)
2.5(0.7-5.6)
0.0001
Total protein g/dl ##
(mean SD)7.48±0.73 7.7±0.56
NS 7.4±0.57 7.5±0.5
NS 7.43±0.7 7.47±0.3
NS
Albumin# g/dl(mean SD)
4.4±0.58 4.8±0.450.0001
4.4±0.5 4.6±0.480.0001
4.28±0.42 4.68±0.370.0001
The correlations between the anthropometric and laboratory parameters and IL-6 190 genotype
Results - polymorphisms
• The polymorphism of the gene IL-6 190 T/C was correlated with anthropometric and paraclinical parameters:
MUAC and TST had statistically significantly higher values in the obese group for the IL-6 190 CC, CT and TT haplotypes (p=0.0001)
the same has been observed for albumins as biochemical parameters
Results
• we observed a very low TT percentage (11.45%) and a high percentage of the CT and CC alleles (88.53%) in the obese group
the C carriers IL6-190 increased in frequency in the obese group
• with significant p of 0.04 (OR=2.3, 95% CI=1.06–4.9)
• There are significant statistical differences between the study group and the control one regarding
– the anthropometric parameters (WHA, MUAC, TSF)
• much more higher values in the obese comparatively with the control group
– biochemical parameters
• It can be observed that the values of glycemia and cholesterol are significantly higher in children with obesity comparatively with the control group
Results
Conclusions
•C carriers IL-6 190 were increased in frequency in the obese group, with a significant p of 0.04
•CT heterozygotes were the most frequent genotypes in the obese children
•BMI, MUAC, TST, and serum albumin levels correlate with the IL-6 190 C alleles in children with obesity
•The polymorphism of the gene IL-6 190 T/C may modulate genes to determine the nutritional status and may be associated with the risk of developing obesity