الفهرس 
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Abstract
Background: Haptoglobin (Hp) is an acute-phase protein that is crucial for the neutralization of oxidative damage and the elimination of free hemoglobin (Hb).
Objectives: The current study aimed to examine the distribution pattern of haptoglobin polymorphism, to elucidate the impact of haptoglobin polymorphism on the genetic expression of CD163 receptors, to find out how genetic polymorphism effects the anthropometric variable, genetic, metabolic and inflammatory aspects related to obesity, and, finally, to investigate how dietary modifications (presented in terms of IF practiced during Ramadan month) could impact the patterns of gene expressions and their consequent metabolic, anthropometric, and inflammatory aspects related to obesity among the recruited overweight and obese subjects.
subjects and Methods: A total of 114 overweight and obese subjects (75 males and 39 females, 38.7 ± 11.7 years) with a mean body mass Index (BMI) of 30.41± 5.09 kg/m2 were recruited in an observational study over two years during Ramadan fasting month. Anthropometric (body weight, height, BMI, visceral fat surface area, muscle, and fat masses), dietary (full macro- and micro-nutrients intake using 24-hour food recall for three days), haptoglobin polymorphism, gene expression of CD163, TFAM, SOD2, Nrf2. SIRT1, SIRT3, biochemical (glucometabolic markers, cardiometabolic markers, and serum CD163), and inflammatory (TNF-α, IL-6) as well as anti-inflammatory (IL-10) biomarkers were assessed before and at the end of the fourth week of the fasting month.
Results: Haptoglobin polymorphisms were determined in 114 overweight and obese subjects, with Hp 2-2 was the most frequently abundant (48.24 %, n = 55) phenotype among the study subjects, followed by the polymorphism Hp 2-1 (46.5 %, n=53), and polymorphism Hp 1-1 (5.26 %, n=6). No significant differences were found between the three Hp polymorphism phenotypes with respect to the anthropometric measurements, while subjects with Hp 1-1 polymorphism showed a significantly higher serum haptoglobin levels than those with Hp2-2 polymorphism counterparts. Further, subjects with Hp 2-1 polymorphism phenotype expressed a significantly higher levels in IL-6 and IL-10 than their counterpart subjects with Hp 2-2 polymorphism phenotype. Alongside, subjects with Hp 2-1, Hp 2-2 polymorphism showed significantly higher levels of insulin resistance, Total cholesterol, LDL- C and triglycerides levels than those with Hp1-1 polymorphism. Also, extremely significant reductions in body weight, BMI, body fat percent, fat mass, fat-free mass, muscle mass, visceral fat area, waist circumference, and hip circumference were found at the end of Ramadan fasting month when compared with the pre-fasting levels. Significant reduction was recorded in insulin sensitivity and insulin-like growth factor, alongside with significant decrease in total cholesterol, triglycerides, and LDL was registered. In contrast, a significant increase in HDL was reported at the end of Ramadan in comparison to the pre-fasting levels. A significant reduction was found in serum haptoglobin while serum CD163 levels presented significantly higher levels at the end of RIF among the study subjects. Moreover, significantly lowered values of IL-6 and TNF-α were observed at the end of Ramadan when compared to the values before, while IL-10 showed a significantly higher levels at the end of Ramadan in comparison with the pre-fasting values. Gene expressions showed highly significant increase for the CD163, Nrf2, SOD2 and TFAM genes while SIRT3 showed significant downregulation among the fasting study subjects at the end of RIF in comparison with the pre-fasting levels.
Conclusion: Haptoglobin polymorphism represents a major factor affecting CD163 receptors among the overweight and obese subjects, withn consequent impact on the metabolic, inflammatory and genetic characteristics of the overweight and obese subjects. The present findings also supported the proposed association of Hp polymorphism, inflammatory cytokines, and serum Hp with lipid profiles and CD163 gene expression in obese individuals. Hp polymorphism and serum Hp might offer a predictive marker for diabetes and cardiovascular diseases. Intermittent fasting practiced during Ramadan significantly and variably affects the metabolic, inflammatory, and genetic markers in relation to Hp polymorphisms.