الفهرس 
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Abstract
Obesity is a multifactorial disease and considered a global concern due to
its increase prevalence globally between adults and children, as it is expected that
more than 50% of the worldwide population could be obese or overweight by
2030.
Obesity also has a major effect on health, as it could lead to degenerative
diseases such as Diabetes type 2 (DT2) fatty liver, cardiovascular diseases and
some sorts of cancers .
Obesity is highly prevalent in Egypt, and as per the WHO statistics the
estimated prevalence of overweight and obesity (BMI ≥ 25 kg/m2) is 61–70% of
the whole population aged 20 and above, with percentage 65% of males and 76%
of females aged 15 and above .
Genetics play an important role in the inception of obesity, as many studies have revealed that polymorphisms of some genes are correlated with a
predisposition to obesity.
FTO (fat mass and obesity associated) gene was first exposed in a genome
wide association study (GWAS) for its contribution in early onset of obesity and
Body Mass Index (BMI) in different populations.
FTO gene is located at 16q12.2 and it encodes a demethylation enzyme
which cleaves the methyl groups from DNA and RNA nucleotides, and it may be
involved in physiological procedures such as the control of energy homeostasis,
DNA methylation, and abiogenesis.
However, its role in the pathophysiology of obesity still under exploration.
This work aimed to study the distribution of FTO gene rs17817449 SNP
and the association of these variants with the clinical and laboratory findings in
Egyptian obese children.
The present study was carried out on eighty children (66 obese and 14 overweighted)
attended to our pediatric genetic & endocrinology unit and clinic in
Menoufia University Hospital.
Eighty apparently healthy children matched with these patients in the same
age and sex from our pediatric general ward in Menoufia University Hospital as
a control group.
The obese children:-
Included 60 females and 20 males, their ages ranged from 6 year to 18
years with mean age of (12.40 ± 3.04)
All patients and Control were subjected to the following after taking Informed
consent:
1. Detailed history taking.
2. Complete general examination: including Anthropometric
measurements (weight, height, WC, Hip C, WHR, BMI, BMI Zscore).
3. Laboratory investigations including:
Fasting blood glucose level.
Postprandial plasma glucose level.
Fasting insulin level.
Insulin resistance :Estimated by Quantitative insulin sensitivity
check index (QUICKI)<0.339 indicate insulin resistance
4. Molecular study of FTO Gene Polymorphism by PCR.
5. Family counselling.
6. Data management and statistical analysis.
This study revealed that:
Consanguinity in obese group was 32.5% this was found to be significant
statistically (p=0.046) compared to controls, Family history of obesity was positive in 77.5% of obese group versus 20% in control group with highly statistically
significant difference (p<0.001) between both groups Family history of T2D was
positive in 37.5% in obese group against 17.5% in control group with statistically
significance.
Anthropometric indexes shows positive statistically significant difference
with weight (P<0.001), WC. (P<0.001), HC (P<0.001), WHR (P<0.007), BMI
(P<0.001) and BMI Z-score (P<0.001).
Laboratory data of the studied groups, showed higher level of fasting blood
sugar (mean 110.73 ± 12.85 mg/dl) and PPG (176.30 ± 18.07 mg/dl) in obese group
than in control group, which was highly statistically significant difference between
cases and controls, (P <0.001).
Fasting insulin was (6.23 ± 1.69) in obese group versus (4.04 ± 0.51) in
control group which is statistically highly significant associations (P <0.001),
QUICKI in obese group was (0.36 ± 0.02) and in control was (0.38 ± 0.01) show
also highly significant association (P <0.001), with positive insulin resistance in
cases 32.5%.
FTO rs17817449 polymorphism genotyping revealed that variants carry
the risk allele G show statistically significant association with obesity in
comparison to T allele.
On the other hand, association was found between FTO gene rs17817449
GG variant and Consanguinity, family history of obesity and of T2D.
As supported by statistical significant there is association between G allele
and WC, BMI, BMI z-score, fasting blood glucose, fasting insulin and QUICKI index for insulin resistence.
In terms of prediabetes risk we revealed that fasting glucose, PPG and fasting
insulin show statistically significant risk for T2D risk, despite non-significance
of rs17817449 SNP and prediabetes risk, the indirect effect through the highly significance association of the SNP and BMI and its influence on fasting insulin
which affect insulin resistance is itself risk for developing type 2 diabetes later
on.