الفهرس 
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Abstract
Obesity is considered a medical condition involving an accumulation of
excess body fat and it may have an adverse effect on health, leading to reduce
life expectancy and increased health problems. The prevalence of obesity is
increasing worldwide at an alarming rate in both developing and developed
countries. It has become a serious epidemic health problem, estimated to be
the fifth leading cause of mmiality at global level. Central adiposity is
associated with metabolic and cardiovascular diseases. The amount of
abdominal fat can be assessed by waist circumference. Waist circumference
correlates positively with abdominal fat content. The waist circumference is
measured in the horizontal plane midway in the distance of superioriliac crest
and the lower margin of the last rib. Execessive body weight associated
vanous disease particularly cardiovascular disease diabetes mellitus type 2
obstructive sleep apnea and osteoarthritis. As a result, obesity has been found
to reduce life expectancy. Also it associated certain cancer.
The human FTO gene was assigned to chromosome 16 at position q12.2.
FTO has a total length of 410509 bp and contains nine exons and several
nucleotide bolymorphism. The FTO gene encodes a 505 amino acid protein.
The human FTO protein shares sequences homologues with the non-heme
ferrous iron Fe(II), and 2-oxoglutarate (0G)-dependent oxygenase (nonhemedioxygenase
superfamily). The FTO gene encodes a 505 amino acid
protein. The human FTO protein shares sequences homologues with the nonheme
ferrous iron Fe(II), and 2-oxoglutarate (0G)-dependent oxygenase
(non-hemedioxygenase superfamily).
The aim of this study is to investigate the association of common
variants of fat mass and obesity associated gene including rs 9939609 and rs
1421085 polymorphisms with obeses and diabetic obeses among Egyption women. The relationship between these genetic variants and clinical
characteristics of cases was also studied.
In addition, using accurate methods of molecular biology techniques
such as PCR-restriction fi-agment length polymorphisms (PCR-RPLPs) for
mutations characterization. Estimation of risk of the disease related to these
mutations comparing the frequency of mutation among obeses cases to
normal populatin controls in Egypt.
This work was in the form of case 105 cases presenting obeses cases and
diabetic obese cases 55 cases obese only. Their mean * D age *36.07 *lo,
range of 14 - 61 year and 50 cases presenting diabetic obeses withmean + D
age 38.94 +I1 and comparing with 100 healthy control are collecting from the
central area of Nile Delta of Egypt from the Departmentobesity and Diabetes
International Medicine Specialized Hospital, Mansoura University, Egypt,
and comparing cases to their complication with length, weight, cholesterol
triglycerides, LDL, HDL, HbAIc, FBG, Insulin, Homa IR, BMI. For all cases
and controls; DNA extraction was carried out followed by PCR detection of
their rs 1421085 and 9939609 genetic polymorphism.
In the first part of our study we have compared of FTO rs 9939609
polymorphic forms in total obese cases compared to controls and adjusted by
age we showed significantly higher frequency of the AA geno type compared
to controls (21.9% vs. 496, OR = 4.99, 95% CI, p = 0.0001). Also, it is found
a strong association in total obese cases compared to control adjusted by
diabetes and age was showed significantly frequency of AA genotype
compared with controls (21.9% vs. 4%, OR = 4.64, p = 0.012) in codominant
model.
On the ather hand, our study did not appear to influence any lipid
parameter in the subject tested include (cholesterol, Trighcerds HDL and
LDL) as well as laboratory tests of diabetes (HbAlc, FBG, insulin and Homa IR) in all obese cases of FTO rs 9939609 gene. Only FTO rs 9939609 gene
showed fasting blood glucose was significantly higher in TT genotype than
TA genotype, p = 0.04%). Therefore, our study reported that strong
association of FTO rs 9939609 and T2DM. Also There is no significant of
BMI and WHR in this study of FTO rs 9939609 gene polymorphism in
obases and obases diabetic case adjusted by age.
In case of demographic and laboratory data of obese non-diabetic cases
compared to controls. Values corresponding to length, weight, cholesterol,
triglycerdies, LDL, insulin, Homa IR, waist, hp and BMI were significantly
higher in cases compared to controls (p<0.05); where as both groups showed
no significant difference regarding their age, waist hip ratio, FBG and HbAlc
(p>0.05).
On the other hand, the frequency of FTO rs 9939609 polymorphic forms
in total obese cases showed a significantly lower frequency of TA genotype in
the over dominant model (35.2% vs. 6096, OR=0.41, 95%CI=0.32-0.74,
p=0.0026).
Frequency of FTO rs1421085 polymorphic genotypes in total obese
cases compared to controls adjusted by age shows the. Obese cases showed
significantly higher frequency of the CC genotype compared to controls
(29.5% vs. 396, OR=20.87, 95%CI= 5.85-74.5, p<=0.0001). Cases have
shownalso a significantly higher frequency of the C allele (48% vs. 18%,
OR=4.37, 95%CI=2.8-6.8, p<0.00001).
The frequency of FTO rs1421085 polymorphic forms in total obese
cases compaed to controls adjusted by diabetes and age. Obese cases showed
significantly higher frequency of the CC genotype compared to controls
(29.5% vs. 3%, OR=22.86, 95%CI= 6.09-85.85, p<=0.0001). This was also
observed but to a lesser degree for the CT genotype (37.1% vs. 29%,
OR=2.21, 95%CI= I .O 1-4.82, p=0.0001) in the codominant model. The same was also observed in the recessive model for the CC genotype (OR=16.78,
95%CI=4.67-60.26, p=0.0001) and in the dominant model for the CT+CC
genotypes (66.7% vs. 32%, OR=4.13, 95%CI= 2.06-8.29, p=0.0001).
In case of laboratory parameters related to lipid profile and blood sugar
in all obese cases regarding their FTO rs9939609 gene polymorphic types.
Cases showed no significant difference for all values of lipid profile
(cl~olesterols, triglycerides, HDL and LDL) as well as laboratory tests of
diabetes (HbAlc, FBG, insulin and Homa IR) related to their polymorphic
genotypes. Also no significan BMI and WHR related to their polymorphic
genotypes. The laboratory parameters related to lipid profile and blood sugar
in all obese diabetic cases regarding their FTO rs1421085 gene polymorphic
types shows laboratory parameters related to lipid profile and blood sugar in
all obese diabetic cases regarding their FTO rs1421085 gene polymorphic
types. Cases showed no significant difference for all values of lipid profile
(cl~olesterols, triglycerides, HDL and LDL) as well as laboratory tests of
diabetes (HbAlc, FBG, insulin and Homa IR) related to their polymorphic
genotypes.
from this study, we can conclude that; cases of FTO investigated
significant and association of FTO rs 9939609 and rs 1421085 polymorphism
with obesity and diabetes type two among cases compared to contrGle
adjusted by age and its correlation with higher fasting glucose in diabetic
obese cases independently from BMI and WIR. On the other hand, no
significant differences of lipid profile and BMI, WHR as well as no
significant of laboratory test of diabetes as HbAl c and HomaIR.
Analysis of these FTO rs 9939609 and rs 1421085 gene polymorphism
among obase case especially familial relationship with obesity to prevent
obeisty and diabetic development.