Sarah El Hajj Chehadeh1, Wael Osman2, Suna Nazar1, Laila Jerman1, Ameera Alghafri3, Ali Sajwani3, Mohamed Alawlaqi4, Mohamed AlObeidli5, Herbert F Jelinek6, Fatme AlAnouti7, Kinda Khalaf8, Habiba Alsafar9. 1. Center for Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates. 2. Center for Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates; College of Arts and Sciences, Khalifa University, Abu Dhabi, United Arab Emirates. 3. College of Medicine, Mohammad Bin Rashid University of Medicine and Health Sciences, Dubai, United Arab Emirates. 4. School of Medicine, The Royal College of Surgeons, Dublin, Ireland. 5. College of Medicine and Health Sciences, United Arab Emirates University, AlAin, United Arab Emirates. 6. School of Community Health, Charles Sturt University, Albury, Australia; Department of Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates. 7. College of Natural and Health Sciences, Zayed University, Abu Dhabi, United Arab Emirates. 8. Department of Biomedical Engineering, Khalifa University, Abu Dhabi, United Arab Emirates. 9. Center for Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates; Department of Genetics and Molecular Biology, College of Medicine and Health Sciences, Khalifa University, Abu Dhabi, United Arab Emirates. Electronic address: habiba.alsafar@ku.ac.ae.
Abstract
OBJECTIVE: Overweight and obesity are major risk factors for Type 2 Diabetes Mellitus (T2DM), cardiovascular disease (CVD) and cancer. Genetic predisposition has been shown to play a key role in obesity, and genome-wide association studies (GWAS) have identified multiple loci linked with obesity in various ethnic groups. The aim of this study was to validate the reported genetic variants associated with obesity and overweight in a young UAE Arab population. METHODS: Twenty-two associated single nucleotide polymorphisms (SNPs) at 11 loci (FTO, MC4R, TMEM18, KCTD15, MTCH2, SH2B1, TFAP2B, GNPDA2, NEGR1, PCSK1 and BDNF) were studied in 392 controls and 318 overweight/obese young Emiratis (aged 18-35 years). RESULTS: After adjusting for age and smoking, rs3751812 of the FTO gene was associated with overweight/obesity in male participants (p-value < 0.016), while SNPs rs17782313, rs571312 of the MC4R gene and rs12463617 of the TMEM18 gene were significantly associated with overweight/obesity in female participants (p-value = 0.001, 0.028, 0.044, respectively). Follow-up association tests and logistic regression revealed the contribution of the FTO rs3751812 and MC4R rs571213 SNPs to the risk of overweight/obesity after adjusting for age, sex and smoking (p-value = 0.044, 0.049, respectively). In addition, the FTO rs3751812 was associated with the risk of overweight/obesity after adjusting for the effect of other markers (rs17782313, rs571312, rs2867125, rs6548238 and rs12463617) (p-value = 0.035). A significant gene-gene interaction was seen between FTO, MCR4 and TMEM18 (p-value = 0.013). CONCLUSIONS: Our data demonstrates that rs3751812 of the FTO gene is the key SNP associated with risk of overweight/obesity among the young UAE Arab population, in alignment with previous findings. Our results also indicate that the identified genes stratify with sex and risk of overweight/obesity. In addition to their direct association with overweight/obesity, rs17782313 and rs571312, as well as rs2867125 and rs6548238, may have a modifying effect on the risk of overweight/obesity caused by the rs3751812. Population-specific, sex-specific genetic profiling is important in understanding the heritability of obesity.
OBJECTIVE: Overweight and obesity are major risk factors for Type 2 Diabetes Mellitus (T2DM), cardiovascular disease (CVD) and cancer. Genetic predisposition has been shown to play a key role in obesity, and genome-wide association studies (GWAS) have identified multiple loci linked with obesity in various ethnic groups. The aim of this study was to validate the reported genetic variants associated with obesity and overweight in a young UAE Arab population. METHODS: Twenty-two associated single nucleotide polymorphisms (SNPs) at 11 loci (FTO, MC4R, TMEM18, KCTD15, MTCH2, SH2B1, TFAP2B, GNPDA2, NEGR1, PCSK1 and BDNF) were studied in 392 controls and 318 overweight/obese young Emiratis (aged 18-35 years). RESULTS: After adjusting for age and smoking, rs3751812 of the FTO gene was associated with overweight/obesity in male participants (p-value < 0.016), while SNPs rs17782313, rs571312 of the MC4R gene and rs12463617 of the TMEM18 gene were significantly associated with overweight/obesity in female participants (p-value = 0.001, 0.028, 0.044, respectively). Follow-up association tests and logistic regression revealed the contribution of the FTOrs3751812 and MC4Rrs571213 SNPs to the risk of overweight/obesity after adjusting for age, sex and smoking (p-value = 0.044, 0.049, respectively). In addition, the FTOrs3751812 was associated with the risk of overweight/obesity after adjusting for the effect of other markers (rs17782313, rs571312, rs2867125, rs6548238 and rs12463617) (p-value = 0.035). A significant gene-gene interaction was seen between FTO, MCR4 and TMEM18 (p-value = 0.013). CONCLUSIONS: Our data demonstrates that rs3751812 of the FTO gene is the key SNP associated with risk of overweight/obesity among the young UAE Arab population, in alignment with previous findings. Our results also indicate that the identified genes stratify with sex and risk of overweight/obesity. In addition to their direct association with overweight/obesity, rs17782313 and rs571312, as well as rs2867125 and rs6548238, may have a modifying effect on the risk of overweight/obesity caused by the rs3751812. Population-specific, sex-specific genetic profiling is important in understanding the heritability of obesity.