الفهرس 
Introduction and aim of the work
Obesity and overweight.Only 14 pages are availabe for public view
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Abstract
Obesity is a leading preventable cause of death worldwide. It is one of the most serious public health problems of the 21st century,women is more common to prone obesity than men.
It is a major risk factor for chronic diseases and plays a central role in the insulin resistance or metabolic syndrome, which includes hyperinsulinemia, hypertension, hyperlipidemia, type II diabetes mellitus, and an increased risk of atherosclerotic cardiovascular disease.
The pathophysiology of obesity iscomplicated; it is caused by a combination of excessive food intake, lack of physical activity, hormonal factors and genetic susceptibility. A few cases are caused primarily by genes, endocrine disorders, medications, or mental illness.
The feelings of hunger and satiety are stimulated by the “gut-brain axis”, where a crucial role is played by gastrointestinal hormones as ghrelin which is produced mainly by ghrelinergic cells in the stomach and involved in both the long-term regulation of body weight and the short-term regulation of postprandial satiety. It functions as a neuropeptide in the central nervous system. Besides regulating appetite, it also plays a significant role in regulating the distribution and rate of use of energy.
The visceral adipose tissue-derived serine protease inhibitor (vaspin) is a new adipocytokine with insulin-sensitizing activity originally identified in visceral adipose tissues of obesity-related type II diabetic rats.Vaspin has multiple physiological roles such as improving glucose tolerance, increasing insulin sensitivity, blood glucose level and acting as an anti-inflammatory mediator in animal or in vitro studies. It may share as a compensatory mechanism in response to the decreased insulin sensitivity.
C-reactive protein (CRP) is one of the strongest markers of chronic inflammation.Adipose tissue is an important source of circulating CRP, Studies have shown that increased body adiposity among adults is associated with higher serum hs-CRP concentrations compared to normal weight individuals .
FTO is one of the genes known to contribute to polygenic obesity; it worked in the brain to increase appetite.Previous studies have identified the genetic variants in the FTO gene are associated with measures of adiposity.
The aim of this present study is toassess the contribution of FTO rs17817449 gene variants towards obesity and diabetes development and evaluate the role of some adipokines like vaspin, and some pro-inflammatory markers as hs-CRP on the outcome of obesity diseases , and to clarify the role of ghrelin hormone as a marker related to obesity , then to study the correlation between all these markers and FTO gene rs17817449 T/G single nucleotide polymorphism as a risk factor for obesity ,beside its relation to the metabolic syndrome (MS) susceptibility in Upper Egyptian obese women .
This study includes: 229 participants, 115 obese womenbesides 114 age matched controls. Obese women were subdivided according to the presence or absence of diabetes mellitus, into2 subgroups:
1) group IA: included 50 obese with DM, their age ranged between 18 to 50 with a mean ± SD of 43.94 ± 4.37.
2) group IB: included 65 obese without DM, their age ranged between 18 to 50 with a mean ± SD of 36.461± 11.59.
The diagnosis of patients depends on BMI of ≥30 kg/m2 with a mean ± SD of 36.45 ± 5.67 according to the definition of obesity by World Health Organization, 2000.
All the anthropometric parameters of obese patients were significantlyhigherin obese patients when compared to the controls as the weight, height, BMI, fat proportion,waist, hip circumference and waist / hip ratio. A significant differences in between the two obese sub groups also found as regards BMI.
There were a significant increase in serum vaspin and hs-CRP levels in obese patients as compared with controls,and between the control group and both obese subgroups (with and without DM).On the other hand, there is a significant decrease in the serum levels of ghrelin in obese patients as comparedto controls, with a significant differences also, between the obese subgroups and controls .Non significant difference between the two obese subgroups as regards serum vaspin ,hs-CRP nor ghrelin were found.
In the current study , a significant increase in the mean levels of biochemical parameters concerning with the susceptibility of MS , in obese women and their subgroups as compared to the controls ,where the mean±SD of systolic and diastolic blood pressure, serum total cholesterol, LDL-ch, triglycerides ,glucose ,insulin and HOMA-IR values were significantly higher in than controls. Higher values were also, observed in both obese subgroups than controls,while there were significant difference between obese patient with and without DM as regards serum total cholesterol,glucose and HOMA-IR values
Serum insulin and HOMA-IR were significantly elevated in ascending order with the highest mean levels in obese with DM group indicating insulin resistance. In addition, it was observed that serum ALT levels were significantly increased in obese patients when compared to the controls which may indicate steatosis.
The higher insulin levels in obese groups, in the current study, were negatively correlated with weight, height and fat proportion. Whereas, is positively correlated with HOMA-IR and serum vaspin levels .
Correlations between the various studied biochemical parameters in the obese group showed a highly significant positive correlation between serum vaspin level and each of serum hs-CRP and serum insulin levels, which indicates a compensatory mechanism for vaspin to normalize the glucose level, and to modify other mediators involved in insulin resistance and inflammatory process as TNF-α.
In addition, a significant negative correlation between serum vaspin and ghrelin were found. This could be a protective mechanism to overcome the low grade inflammatory state of obesity where any one of them may act as an anti-inflammatory mediator.
In the present study the distribution of different genotyping and alleles frequencies of FTO rs17817449 (T/G)SNP was significantlyassociatedamong both control and obese groups. Hardy –Weinberg equation for these observed genotyping among obese patient showed that the observed genotyping is consistent with HWE.
TTis the normal variant for this SNP, the distribution of the homozygous variant GG and heterozygous variant GT is more in obese group, however TT genotyping is more distributed in controls, G allele (the minor allele) is more frequent in obese subjects and itsfrequency is 46.5% among obese women versus 33.3%among controls.This is to say that, G allele carriers were at risk 1.739 times more than T carriers, and the homozygous (GG) genotypes were at risk 2.535 times and the heterozygous (GT)were at risk 1.734 times for obesity more than TT carriers. Also, in this current study,The FTO rs 17817449 T/G polymorphism was significantly associated with obesity risk in both the dominant (GT +GG vs. TT) and recessive (GG vs. TT+GT) tested inheritance models (OR 1.965 and 1.924 respectively).
Moreover, The associations analysis of FTO rs17817449 T/G SNP in controls and obese subgroups in this present study revealed, also, that the G allele frequency among obese non diabetics and obese diabetics subgroups are (47.7% and 45% respectively) versus 33.3%among controls.Also,the G allele carriers were significantly at risk 1.82 times more than T carriers in both subgroups, and the homozygous (GG) genotypes were significantly at risk 2.75 times for obesity more than TT carriers in obese without DM subgroup. Again, in this current study, The FTO rs17817449 T/G polymorphism was significantly associated with obesity risk 2.097 times in the dominant (GT +GG vs. TT) tested inheritance models.
On the other hand, in this current study, there were no significant associations in the genotyping or allelic frequency associations analysis for the same SNP FTO rs17817449T/G in between the obese subgroups, data of dominant, recessive or additive tested inheritance models showed that the risk associations not reach significant levels.
While there is a significant associationin obese group between homozygous TT carriers and theGGcarriers as regards BMI, waist and hip circumferences. Also, the data of the present study, revealed that, the carriers of allele T allele in its homozygous state, might be associated with a lower BMI, weight, fat percentage and smaller waist and hip circumferences in all groups so , have a decreased risk for obesity and metabolic syndrome. To the best of our knowledge, this is the first study for FTO gene polymorphism among Upper Egyptian women. The current study provides evidence that the FTO SNP is a potential indicator for obesity susceptibility because it is strongly associated with several measures of adiposity. Further studies with a larger sample size are needed to verify these results.