Cyrus Cyril, Ismail Mona H, Chathoth Shahanas, Vatte Chittibabu, Hasen Majd, Al Ali Amein
1 Department of Genetic Research, Institute for Research and Medical Consultation, Imam Abdulrahman Bin Faisal University , Dammam, Saudi Arabia .
2 Department of Internal Medicine, King Fahd Hospital of the University, Imam Abdulrahman Bin Faisal University , Al-Khobar, Saudi Arabia .
Genet Test Mol Biomarkers. 2018 Mar;22(3):170-177. doi: 10.1089/gtmb.2017.0218. Epub 2018 Feb 21.
Obesity has reached epidemic proportions worldwide resulting in a serious public health problem. In Saudi Arabia, 28.7% of the population is obese due largely to the adoption of western dietary patterns over the last decade. The fat-mass and obesity associated (FTO) and melanocortin-4 receptor (MC4R) genes are ubiquitously expressed in the brain and pancreatic islets, and are the main link between the central nervous system and energy homeostasis based on food intake and energy expenditure. Genetic variants in the FTO and MC4R genes have been strongly associated with an increased obesity risk.
To identify novel mutations in the MC4R gene and to perform correlation analyses of the known variants rs9939609 and rs1421085 in the FTO gene and rs17782313 near the MC4R gene in an obese Saudi population.
A total of 136 obese patients and 104 healthy controls from King Fahd Hospital, Al-Khobar, were genotyped for single-nucleotide polymorphisms within or near the FTO and MC4R genes using the TaqMan assay. Leptin levels were determined by enzyme-linked immunosorbent assay. Targeted sequencing of MC4R exon was done by Sanger sequencing method.
The study included 58 obese males and 78 obese females with a mean age of 39.78 ± 12.77 years and a mean body mass index (BMI) of 42.65 ± 9.03 kg/m. A significant increase in the levels of leptin and triglycerides was associated with an increase of BMI. Other factors such as lactate dehydrogenase, gamma-glutamyltransferase, and high-density lipoprotein were also significantly higher in the severely obese cohort. The FTO polymorphisms were associated with a significantly increased risk for obesity and in BMI-stratified cohort, rs9939609 (T/A: odds ratio [OR] = 1.73, p = 0.007) and rs1421085 (T/C: OR = 1.56, p = 0.03) showed even stronger association. Genotyping for the near MC4R polymorphism, rs17782313 revealed an association with moderately obese patients (T/C: OR = 1.73, p = 0.038).
The studied FTO gene polymorphisms were found to be significantly associated with increased BMI and were highly significantly associated with severe obesity. These FTO gene polymorphisms combined with a high-fat diet appear to promote early-onset obesity in the Saudi population. FTO polymorphisms appear to be universally associated with the risk of obesity, and further investigation into this genetic locus may provide clues for potential therapeutic targets.
肥胖在全球范围内已达到流行程度，导致严重的公共卫生问题。在沙特阿拉伯，28.7%的人口肥胖，这主要归因于过去十年中西方饮食模式的采用。脂肪量和肥胖相关（FTO）基因和黑皮质素-4受体（MC4R）基因在大脑和胰岛中普遍表达，是基于食物摄入和能量消耗的中枢神经系统与能量稳态之间的主要联系。FTO和MC4R基因中的遗传变异与肥胖风险增加密切相关。
在肥胖的沙特人群中鉴定MC4R基因的新突变，并对FTO基因中的已知变异rs9939609和rs1421085以及MC4R基因附近的rs17782313进行相关性分析。
从胡拜尔法赫德国王医院选取136例肥胖患者和104例健康对照，采用TaqMan分析法对FTO和MC4R基因内部或附近的单核苷酸多态性进行基因分型。通过酶联免疫吸附测定法测定瘦素水平。采用Sanger测序法对MC4R外显子进行靶向测序。
该研究纳入了58名肥胖男性和78名肥胖女性，平均年龄为39.78±12.77岁，平均体重指数（BMI）为42.65±9.03kg/m²。瘦素和甘油三酯水平的显著升高与BMI的增加相关。其他因素如乳酸脱氢酶、γ-谷氨酰转移酶和高密度脂蛋白在重度肥胖队列中也显著更高。FTO基因多态性与肥胖风险显著增加相关，在按BMI分层的队列中，rs9939609（T/A：比值比[OR]=1.73，p=0.007）和rs1421085（T/C：OR=1.56，p=0.03）显示出更强的相关性。对MC4R基因附近的多态性rs17782313进行基因分型，发现与中度肥胖患者相关（T/C：OR=1.73，p=0.038）。
研究发现FTO基因多态性与BMI增加显著相关，与重度肥胖高度显著相关。这些FTO基因多态性与高脂肪饮食相结合，似乎促进了沙特人群早发性肥胖。FTO基因多态性似乎普遍与肥胖风险相关，对这一基因位点的进一步研究可能为潜在治疗靶点提供线索。
