Bahareh Sedaghati-Khayat1, Maryam Barzin2, Mahdi Akbarzadeh1, Kamran Guity1, Mohammad-Sadegh Fallah3, Hoda Pourhassan4, Fereidoun Azizi5, Maryam S Daneshpour6. 1. Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 19195-4763, Tehran, Islamic Republic of Iran. 2. Obesity Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran. 3. Kawsar Human Genetics Research Center, Tehran, Islamic Republic of Iran. 4. Department of Internal Medicine, University of California Riverside, Riverside, CA, USA. 5. Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, Tehran, Islamic Republic of Iran. 6. Cellular and Molecular Endocrine Research Center, Research Institute for Endocrine Sciences, Shahid Beheshti University of Medical Sciences, PO Box 19195-4763, Tehran, Islamic Republic of Iran. daneshpour@sbmu.ac.ir.
Abstract
BACKGROUND: Obesity is currently an international epidemic and metabolic derangements pose these individuals at greater risk for future morbidity and mortality. Genetics and environmental factors have undeniable effects and among genetic risk factors, FTO/CETP genes are important. The current study examines the interaction between obesity phenotypes and FTO/CETP SNPs and their effects on lipid profile changes. MATERIALS AND METHODS: We selected 954 adult subjects from TCGS (47.9% male). Participants were stratified according to their BMI and presence of metabolic syndrome according to the Joint Interim Statement (JIS) definition. Nine selected polymorphisms from FTO/CETP genes were genotyped using Tetra ARMS-PCR method. After age and sex adjustment the interaction of 9 markers with lipid profiles among phenotypes were tested by PASW. RESULTS: In three main groups, HDL_C level had a strong significant association with CETP markers: (rs3764261, β(95% CI) - 0.48(- 0.61 to - 0.35), P = 1.0 × 10-11), (rs1800775, β(95% CI) 0.5(0.36;0.65), P = 1.0 × 10-6) and (rs1864163, β(95% CI) 0.3(0.16;0.43), P = 9.1 × 10-5). This association was also seen in rs7202116 within the total population. In only unhealthy metabolic obese (MUHO) subgroups four new FTO markers (rs1421085, rs1121980, rs1558902 and rs8050136) (P value < 0.01) demonstrated significant association, even after lipid profile adjustment. CONCLUSION: In the present study, we investigated the association between obesity phenotypes and some variations in FTO/CETP genes for the first time. Our study showed that four markers in the first intron of the FTO gene should be the risk marker in MUHO participants. LEVEL OF EVIDENCE: Level III, case-control study.
BACKGROUND:Obesity is currently an international epidemic and metabolic derangements pose these individuals at greater risk for future morbidity and mortality. Genetics and environmental factors have undeniable effects and among genetic risk factors, FTO/CETP genes are important. The current study examines the interaction between obesity phenotypes and FTO/CETP SNPs and their effects on lipid profile changes. MATERIALS AND METHODS: We selected 954 adult subjects from TCGS (47.9% male). Participants were stratified according to their BMI and presence of metabolic syndrome according to the Joint Interim Statement (JIS) definition. Nine selected polymorphisms from FTO/CETP genes were genotyped using Tetra ARMS-PCR method. After age and sex adjustment the interaction of 9 markers with lipid profiles among phenotypes were tested by PASW. RESULTS: In three main groups, HDL_C level had a strong significant association with CETP markers: (rs3764261, β(95% CI) - 0.48(- 0.61 to - 0.35), P = 1.0 × 10-11), (rs1800775, β(95% CI) 0.5(0.36;0.65), P = 1.0 × 10-6) and (rs1864163, β(95% CI) 0.3(0.16;0.43), P = 9.1 × 10-5). This association was also seen in rs7202116 within the total population. In only unhealthy metabolic obese (MUHO) subgroups four new FTO markers (rs1421085, rs1121980, rs1558902 and rs8050136) (P value < 0.01) demonstrated significant association, even after lipid profile adjustment. CONCLUSION: In the present study, we investigated the association between obesity phenotypes and some variations in FTO/CETP genes for the first time. Our study showed that four markers in the first intron of the FTO gene should be the risk marker in MUHO participants. LEVEL OF EVIDENCE: Level III, case-control study.
Entities:
Keywords:
Cholesteryl ester transfer protein; Fat mass and obesity-associated protein; Metabolic syndrome; Obesity
Authors: Shaun Purcell; Benjamin Neale; Kathe Todd-Brown; Lori Thomas; Manuel A R Ferreira; David Bender; Julian Maller; Pamela Sklar; Paul I W de Bakker; Mark J Daly; Pak C Sham Journal: Am J Hum Genet Date: 2007-07-25 Impact factor: 11.025
Authors: Fereidoun Azizi; Maziar Rahmani; Habib Emami; P Mirmiran; R Hajipour; M Madjid; J Ghanbili; A Ghanbarian; Y Mehrabi; N Saadat; P Salehi; N Mortazavi; P Heydarian; N Sarbazi; S Allahverdian; N Saadati; E Ainy; S Moeini Journal: Soz Praventivmed Date: 2002