Obesity Risk Prediction among Women of Upper Egypt: The impact of FTO rs17817449 gene polymorphism, serum ghrelin and high sensitivity C- reactive protein

Abstract

Obesity is one of the main threats to the human health. It is a major risk factor for hyperinsulinemia, hypertension, hyperlipidemia, type II diabetes mellitus, and atherosclerotic cardiovascular disease. FTO gene variants have been associated with obesity and diabetes mellitus in different populations, but its role in the susceptibility of these diseases remains unknown. The present study is undertaken to assess the contribution of the FTO rs17817449 gene variants towards obesity and diabetes development and to evaluate the role of ghrelin and hs- CRP on the outcome of obesity in the Upper Egyptian women. A total of 229 subjects, 115 obese (65 non diabetics, 50 diabetics) and 114 non obese non diabetic controls were included in this case control study. Genotyping of FTO gene rs17817449 (T>G) polymorphism was performed by mutagenically separated PCR (MS-PCR) method. Estimation of serum gherlin, hs-CRP levels, related anthropometric and metabolic parameters were performed. The results revealed higher frequency of FTO rs17817449 G allele among obese subjects (46.5%) and obese diabetics (45%) compared to the controls (33.3%) which comprise about 1.75 times increase in the risk for obesity (p<0.01). The distribution of the GG and TG genotypes of FTO were 25.2%, and 42.6% among obese non diabetic, 24% and 42% among obese diabetic and 14.9% and 36.8% among controls respectively. FTO-GG genotype variant was significantly associated with weight, BMI and waist and hip circumference (p<0.05 for each). FTO GG carriers had 2.54 times the possibility to have obesity more than TT carriers. Ghrelin levels were significantly decreased and hs-CRP levels were significantly increased in obese subjects compared to the controls (P<0.001 for each). There was a significant negative correlation between serum ghrelin and hs-CRP (p<0.05). No significant association was detected between FTO genotypes and each of ghrelin, hs-CRP, lipid profile, fasting glucose or insulin levels. In conclusion, the G allele of FTO rs17817449 genotyping is associated with increased obesity risk but there is a lack of association with diabetes. It is also associated with some obesity indices as BMI, hip and waist circumference in the Upper Egyptian women. Both Ghrelin and hs- CRP could play a role in developing obesity. To the best of our knowledge, this is the first study of FTO SNP in Upper Egyptian women. Switching off this FTO faulty gene variant by the recent therapies (as certain foods or gene therapy) will prevent the percentage of women who is affected by this risk allele to get obese via burning rather than storing energy.

Key words: FTO gene polymorphism, ghrelin, hs-CRP, Obesity