Center for Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates.
Center for Biotechnology, Khalifa University, Abu Dhabi, United Arab Emirates; College of Arts and Sciences, Khalifa University, Abu Dhabi, United Arab Emirates.
Gene. 2020 May 20;739:144509. doi: 10.1016/j.gene.2020.144509. Epub 2020 Feb 25.
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.
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).
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).
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.
超重和肥胖是 2 型糖尿病（T2DM）、心血管疾病（CVD）和癌症的主要危险因素。遗传易感性已被证明在肥胖中起着关键作用，全基因组关联研究（GWAS）已经确定了多个与不同种族肥胖相关的基因座。本研究旨在验证在年轻的阿联酋阿拉伯人群中与肥胖和超重相关的已报道遗传变异。
在 392 名对照者和 318 名超重/肥胖的年轻阿联酋人（年龄 18-35 岁）中，研究了 11 个基因座（FTO、MC4R、TMEM18、KCTD15、MTCH2、SH2B1、TFAP2B、GNPDA2、NEGR1、PCSK1 和 BDNF）的 22 个相关单核苷酸多态性（SNP）。
在调整年龄和吸烟因素后，FTO 基因的 rs3751812 与男性参与者的超重/肥胖相关（p 值<0.016），而 MC4R 基因的 rs17782313、rs571312 和 TMEM18 基因的 rs12463617 与女性参与者的超重/肥胖显著相关（p 值=0.001、0.028、0.044，分别）。随访关联测试和逻辑回归显示，在调整年龄、性别和吸烟因素后，FTO rs3751812 和 MC4R rs571213 SNP 对超重/肥胖的风险有贡献（p 值=0.044、0.049，分别）。此外，在调整其他标记物（rs17782313、rs571312、rs2867125、rs6548238 和 rs12463617）的效应后，FTO rs3751812 与超重/肥胖的风险相关（p 值=0.035）。FTO、MCR4 和 TMEM18 之间存在显著的基因-基因相互作用（p 值=0.013）。
我们的数据表明，FTO 基因的 rs3751812 是与年轻的阿联酋阿拉伯人群超重/肥胖风险相关的关键 SNP，与先前的研究结果一致。我们的结果还表明，所确定的基因与性别和超重/肥胖风险有关。除了与超重/肥胖直接相关外，rs17782313 和 rs571312 以及 rs2867125 和 rs6548238 可能对 rs3751812 引起的超重/肥胖风险具有修饰作用。特定人群、特定性别的遗传特征分析对于理解肥胖的遗传性很重要。
