PDF(Pubmed)
Abstract：
UNASSIGNED: Obesity is a multifactorial disease associated with the development of many comorbidities. This disease is associated with several metabolic alterations; however, it has been shown that some individuals with obesity do not exhibit metabolic syndrome. Adipose tissue neutralizes the detrimental effects of circulating fatty acids, ectopic deposition, and inflammation, among others, through its esterification into neutral lipids that are stored in the adipocyte. However, when the adipocyte is overloaded, i.e., its expansion capacity is exceeded, this protection is lost, resulting in fatty acid toxicity with ectopic fat accumulation in peripheral tissues and inflammation. In this line, this study aimed to investigate whether polymorphisms in genes that control adipose tissue fat storage capacity are potential biomarkers for severe obesity susceptibility and also metabolic complications.
UNASSIGNED: This study enrolled 305 individuals with severe obesity (cases, BMI≥35 kg/m2) and 196 individuals with normal weight (controls, 18.5≤BMI≤24.9 kg/m2). Demographic, anthropometric, biochemical, and blood pressure variables were collected from the participants. Plasma levels of leptin, resistin, MCP1, and PAI1 were measured by Bio-Plex 200 Multiplexing Analyzer System. Genomic DNA was extracted and variants in DBC1 (rs17060940), SIRT1 (rs7895833 and rs1467568), UCP2 (rs660339), PPARG (rs1801282) and ADRB2 (rs1042713 and rs1042714) genes were genotyped by PCR allelic discrimination using TaqMan® assays.
UNASSIGNED: Our findings indicated that SIRT1 rs7895833 polymorphism was a risk factor for severe obesity development in the overdominant model. SIRT1 rs1467568 and UCP2 rs660339 were associated with anthropometric traits. SIRT1 rs1467568 G allele was related to lower medians of body adipose index and hip circumference, while the UCP2 rs660339 AA genotype was associate with increased body mass index. Additionally, DBC1 rs17060940 influenced glycated hemoglobin. Regarding metabolic alterations, 27% of individuals with obesity presented balanced metabolic status in our cohort. Furthermore, SIRT1 rs1467568 AG genotype increased 2.5 times the risk of developing metabolic alterations. No statistically significant results were observed with Peroxisome Proliferator-Activated Receptor Gama and ADRB2 polymorphisms.
UNASSIGNED: This study revealed that SIRT1 rs7895833 and rs1467568 are potential biomarkers for severe obesity susceptibility and the development of unbalanced metabolic status in obesity, respectively. UCP2 rs660339 and DBC1 rs17060940 also showed a significant role in obesity related-traits.
UNASSIGNED: This study enrolled 305 individuals with severe obesity (cases, BMI≥35 kg/m2) and 196 individuals with normal weight (controls, 18.5≤BMI≤24.9 kg/m2). Demographic, anthropometric, biochemical, and blood pressure variables were collected from the participants. Plasma levels of leptin, resistin, MCP1, and PAI1 were measured by Bio-Plex 200 Multiplexing Analyzer System. Genomic DNA was extracted and variants in DBC1 (rs17060940), SIRT1 (rs7895833 and rs1467568), UCP2 (rs660339), PPARG (rs1801282) and ADRB2 (rs1042713 and rs1042714) genes were genotyped by PCR allelic discrimination using TaqMan® assays.
UNASSIGNED: Our findings indicated that SIRT1 rs7895833 polymorphism was a risk factor for severe obesity development in the overdominant model. SIRT1 rs1467568 and UCP2 rs660339 were associated with anthropometric traits. SIRT1 rs1467568 G allele was related to lower medians of body adipose index and hip circumference, while the UCP2 rs660339 AA genotype was associate with increased body mass index. Additionally, DBC1 rs17060940 influenced glycated hemoglobin. Regarding metabolic alterations, 27% of individuals with obesity presented balanced metabolic status in our cohort. Furthermore, SIRT1 rs1467568 AG genotype increased 2.5 times the risk of developing metabolic alterations. No statistically significant results were observed with Peroxisome Proliferator-Activated Receptor Gama and ADRB2 polymorphisms.
UNASSIGNED: This study revealed that SIRT1 rs7895833 and rs1467568 are potential biomarkers for severe obesity susceptibility and the development of unbalanced metabolic status in obesity, respectively. UCP2 rs660339 and DBC1 rs17060940 also showed a significant role in obesity related-traits.
摘要：
■肥胖是一种与许多合并症的发展有关的多因素疾病。这种疾病与几种代谢改变有关；然而，研究表明，一些肥胖患者没有表现出代谢综合征。脂肪组织中和循环脂肪酸的有害影响，异位沉积,和炎症，其中,通过其酯化成储存在脂肪细胞中的中性脂质。然而,当脂肪细胞过载时，即，超出了它的扩展能力，这种保护失去了，导致脂肪酸毒性与周围组织异位脂肪堆积和炎症。在这行,本研究旨在调查控制脂肪组织脂肪储存能力的基因多态性是否是严重肥胖易感性和代谢并发症的潜在生物标志物.
■这项研究纳入了305名重度肥胖患者(病例，BMI≥35kg/m2）和196名体重正常的个体（对照，18.5≤BMI≤24.9kg/m2)。人口统计,人体测量学,生物化学，并收集参与者的血压变量.血浆瘦素水平,抵抗素,通过Bio-Plex200多路复用分析仪系统测量MCP1和PAI1。提取基因组DNA并在DBC1（rs17060940）中变异，SIRT1（rs7895833和rs1467568），UCP2(rs660339),PPARG(rs1801282)和ADRB2(rs1042713和rs1042714)基因通过使用TaqMan®测定的PCR等位基因鉴别进行基因分型。
■我们的发现表明SIRT1rs7895833多态性是超显性模型中严重肥胖发展的危险因素。SIRT1rs1467568和UCP2rs660339与人体测量学性状相关。SIRT1rs1467568G等位基因与体脂指数和臀围的中位数较低有关，而UCP2rs660339AA基因型与体重指数增加有关。此外,DBC1rs17060940影响糖化血红蛋白。关于代谢改变，在我们的队列中，27%的肥胖个体呈现平衡的代谢状态。此外，SIRT1rs1467568AG基因型增加了发生代谢改变的风险的2.5倍。过氧化物酶体增殖物激活受体Gama和ADRB2多态性未观察到统计学上的显着结果。
■这项研究表明，SIRT1rs7895833和rs1467568是严重肥胖易感性和肥胖代谢失衡发展的潜在生物标志物，分别。UCP2rs660339和DBC1rs17060940在肥胖相关性状中也显示出显着作用。
■这项研究纳入了305名重度肥胖患者(病例，BMI≥35kg/m2）和196名体重正常的个体（对照，18.5≤BMI≤24.9kg/m2)。人口统计,人体测量学,生物化学，并收集参与者的血压变量.血浆瘦素水平,抵抗素,通过Bio-Plex200多路复用分析仪系统测量MCP1和PAI1。提取基因组DNA并在DBC1（rs17060940）中变异，SIRT1（rs7895833和rs1467568），UCP2(rs660339),PPARG(rs1801282)和ADRB2(rs1042713和rs1042714)基因通过使用TaqMan®测定的PCR等位基因鉴别进行基因分型。
■我们的发现表明SIRT1rs7895833多态性是超显性模型中严重肥胖发展的危险因素。SIRT1rs1467568和UCP2rs660339与人体测量学性状相关。SIRT1rs1467568G等位基因与体脂指数和臀围的中位数较低有关，而UCP2rs660339AA基因型与体重指数增加有关。此外,DBC1rs17060940影响糖化血红蛋白。关于代谢改变，在我们的队列中，27%的肥胖个体呈现平衡的代谢状态。此外，SIRT1rs1467568AG基因型增加了发生代谢改变的风险的2.5倍。过氧化物酶体增殖物激活受体Gama和ADRB2多态性未观察到统计学上的显着结果。
■这项研究表明，SIRT1rs7895833和rs1467568是严重肥胖易感性和肥胖代谢失衡发展的潜在生物标志物，分别。UCP2rs660339和DBC1rs17060940在肥胖相关性状中也显示出显着作用。
