الفهرس | Only 14 pages are availabe for public view |
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. |