de Oliveira Raquel, Moraes Tamiris Invencioni, Cerda Alvaro, Hirata Mario Hiroyuki, Fajardo Cristina Moreno, Sousa Marcela Correia, Dorea Egidio Lima, Bernik Márcia Martins Silveira, Hirata Rosario Dominguez Crespo
School of Pharmaceutical Sciences, University Sao Paulo, Av. Prof. Lineu Prestes, 580, 05508-900, Sao Paulo, SP Brazil.
School of Pharmaceutical Sciences, University Sao Paulo, Av. Prof. Lineu Prestes, 580, 05508-900, Sao Paulo, SP Brazil ; Center of Molecular Biology and Pharmacogenetics, BIOREN-CEGIN, Universidad de La Frontera, Temuco, Chile.
Diabetol Metab Syndr. 2015 Apr 11;7:34. doi: 10.1186/s13098-015-0027-2. eCollection 2015.
Polymorphisms in genes encoding adiponectin (ADIPOQ) and interleukin-6 (IL6) have been associated with adiposity and obese-related phenotypes. This study investigated the relationship of ADIPOQ and IL6 gene polymorphisms with pro-inflammatory and cardiometabolic markers in obese patients.
Anthropometric and body composition parameters were measured in 249 Brazilian subjects (30 to 68 yr). Metabolic and inflammatory markers and adipokines were analyzed in blood samples. ADIPOQ rs2241766 (45 T > G) and IL6 rs1800795 (-174G > C) polymorphisms were analyzed by real-time PCR and PCR-RFLP, respectively.
Type 2 diabetes, hypertension, dyslipidemia and increased values of waist circumference, body fat, leptin, fibrinogen, IL-1β, hsCRP and TNFα were related to obesity (p < 0.05). Multiple linear regression analysis showed a positive correlation between BMI and waist circumference, body fat, leptin, fibrinogen, PAI-1, IL-1β, hsCRP and TNFα values (p < 0.001) but not with adiponectin. Obese group had altered metabolic status, resistance to leptin and insulin, and atherogenic and pro-inflammatory profiles. ADIPOQ and IL6 variants were not directely related to obesity, leptin resistance or alterations in cardiometabolic markers. Individuals carrying ADIPOQ 45G allele (TG + GG genotype) had higher IL-6, IL-1β and TNFα levels than TT genotype carriers (p < 0.05). IL6 -174GG genotype was associated with increased IL-1β levels (p = 0.033).
Obesity is associated with leptin resistance, cardiometabolic alterations and a pro-inflammatory status. Our results are suggestive that ADIPOQ and IL6 polymorphisms contribute to cardiometabolic risk in obese individuals.
脂联素(ADIPOQ)和白细胞介素-6(IL6)编码基因的多态性与肥胖及肥胖相关表型有关。本研究调查了肥胖患者中ADIPOQ和IL6基因多态性与促炎和心脏代谢标志物之间的关系。
对249名巴西受试者(30至68岁)进行人体测量和身体成分参数测量。分析血样中的代谢和炎症标志物以及脂肪因子。分别通过实时PCR和PCR-RFLP分析ADIPOQ rs2241766(45T>G)和IL6 rs1800795(-174G>C)多态性。
2型糖尿病、高血压、血脂异常以及腰围、体脂、瘦素、纤维蛋白原、IL-1β、hsCRP和TNFα值升高与肥胖有关(p<0.05)。多元线性回归分析显示BMI与腰围、体脂、瘦素、纤维蛋白原、PAI-1、IL-1β、hsCRP和TNFα值之间呈正相关(p<0.001),但与脂联素无关。肥胖组代谢状态改变,对瘦素和胰岛素产生抵抗,具有致动脉粥样硬化和促炎特征。ADIPOQ和IL6变异与肥胖、瘦素抵抗或心脏代谢标志物改变无直接关系。携带ADIPOQ 45G等位基因(TG+GG基因型)的个体比TT基因型携带者具有更高的IL-6、IL-1β和TNFα水平(p<0.05)。IL6 -174GG基因型与IL-1β水平升高有关(p=0.033)。
肥胖与瘦素抵抗、心脏代谢改变和促炎状态有关。我们的结果表明ADIPOQ和IL6多态性在肥胖个体的心脏代谢风险中起作用。