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瘦素通路基因单核苷酸多态性与肥胖相关的人体测量学、生化和饮食标志物的关系。

Association between SNPs in Leptin Pathway Genes and Anthropometric, Biochemical, and Dietary Markers Related to Obesity.

机构信息

Ingeniería en Biotecnología, Facultad de Química, Universidad Autónoma de Querétaro, Querétaro 76010, Mexico.

Médico Cirujano, Centro de Ciencias de la Salud, Universidad Autónoma de Aguascalientes. Av. Universidad #940, Ciudad Universitaria, Aguascalientes 20100, Mexico.

出版信息

Genes (Basel). 2022 May 25;13(6):945. doi: 10.3390/genes13060945.

Abstract

Obesity is one of the main public health problems in Mexico and the world and one from which a large number of pathologies derive. Single nucleotide polymorphisms (SNPs) of various genes have been studied and proven to contribute to the development of multiple diseases. SNPs of the leptin pathway have been associated with the control of hunger and energy expenditure as well as with obesity and type 2 diabetes mellitus. Therefore, the present work focused on determining the association between anthropometric markers and biochemical and dietary factors related to obesity and SNPs of leptin pathway genes, such as the leptin gene (LEP), the leptin receptor (LEPR), proopiomelanocortin (POMC), prohormone convertase 1 (PCSK1), and the melanocortin 4 receptor (MC4R). A population of 574 young Mexican adults of both sexes, aged 19 years old on average and without metabolic disorders previously diagnosed, underwent a complete medical and nutritional evaluation, biochemical determination, and DNA extraction from the blood; DNA samples were subsequently genotyped. Association analyses between anthropometric, biochemical, and dietary variables with SNPs were performed using binary logistic regressions (p-value = 0.05). Although the sampled population did not have previously diagnosed diseases, the evaluation results showed that 33% were overweight or obese according to BMI and 64% had non-clinically elevated levels of body fat. From the 74 SNP markers analyzed from the five previously mentioned genes, 62 showed polymorphisms within the sampled population, and only 35 of these had significant associations with clinical variables. The risk associations (OR > 1) occurred between clinical markers with elevated values for waist circumference, waist−height index, BMI, body fat percentage, glucose levels, insulin levels, HOMA-IR, triglyceride levels, cholesterol levels, LDL-c, low HDL-c, carbohydrate intake, and protein intake and SNPs of the LEP, LEPR, PCSK1, and MC4R genes. On the other hand, the protective associations (OR < 1) were associated with markers including elevated values for insulin, HOMA-IR, cholesterol, c-LDL, energy intake > 2440 Kcal/day, and lipid intake and SNPs of the LEP and LEPR genes and POMC. The present study describes associations between SNPs in leptin pathway genes, revealing positive and negative interactions between reported SNPs and the clinical markers related to obesity in a sampled Mexican population. Hence, our results open the door for the further study of new genetic variants and their influence on obesity.

摘要

肥胖是墨西哥和世界的主要公共卫生问题之一,也是许多疾病的根源。各种基因的单核苷酸多态性(SNPs)已经被研究并证明与多种疾病的发展有关。瘦素途径的 SNPs 与饥饿和能量消耗的控制以及肥胖和 2 型糖尿病有关。因此,本工作重点确定与肥胖相关的人体测量标记物和生化及饮食因素与瘦素途径基因的 SNPs 之间的关系,如瘦素基因(LEP)、瘦素受体(LEPR)、前阿黑皮素原(POMC)、前激素转化酶 1(PCSK1)和黑素皮质素 4 受体(MC4R)。一组 574 名年轻的墨西哥成年人,男女各半,平均年龄 19 岁,没有先前诊断出的代谢紊乱,接受了全面的医学和营养评估、生化测定和血液 DNA 提取;随后对 DNA 样本进行基因分型。使用二元逻辑回归(p 值=0.05)对人体测量、生化和饮食变量与 SNPs 之间的关联进行分析。尽管抽样人群没有先前诊断出的疾病,但评估结果显示,根据 BMI,33%的人超重或肥胖,64%的人体脂肪含量非临床升高。在从前面提到的五个基因中分析的 74 个 SNP 标记中,有 62 个在抽样人群中显示出多态性,只有 35 个与临床变量有显著关联。与临床标志物(如腰围、腰高比、BMI、体脂肪百分比、血糖水平、胰岛素水平、HOMA-IR、甘油三酯水平、胆固醇水平、LDL-c、低 HDL-c、碳水化合物摄入和蛋白质摄入)的升高值相关的风险关联(OR>1)发生在 LEP、LEPR、PCSK1 和 MC4R 基因的 SNP 中。另一方面,与胰岛素、HOMA-IR、胆固醇、c-LDL、能量摄入>2440 Kcal/天、脂质摄入和 LEP 和 LEPR 基因的 SNP 以及 POMC 升高值相关的保护关联(OR<1)与报告的 SNP 之间存在正、负相互作用。本研究描述了瘦素途径基因中 SNPs 之间的关联,揭示了在墨西哥抽样人群中与肥胖相关的临床标志物之间的正、负相互作用。因此,我们的结果为进一步研究新的遗传变异及其对肥胖的影响开辟了道路。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f8f3/9222344/fa57bb6ccdfd/genes-13-00945-g001.jpg

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