冠心病患者MC4R基因突变与血清ADP、LEP及IL-6的关系及意义

Relationship between mutation of MC4R gene and serum leptin, adiponectin and interleukin 6 in patients with coronary heart disease

目的探讨冠心病(CHD)患者黑素皮质素受体4(MC4R)基因rs17782313位点突变与血清瘦素(LEP)、脂联素(ADP)、白介素6(IL-6)的关系及临床意义。方法选取CHD患者416例为观察组,同期正常体检者400例为对照组。采用DNA直接测序技术对入组者的MC4R基因rs17782313(T/C)位点多态性进行检测,按突变情况分为TT、CT、CC三种基因型。酶联免疫吸附试验(ELISA)法检测各基因型血清LEP、ADP、IL-6水平;检测两组的血脂、体质量指数(BMI)等指标。逐步回归分析统计MC4R基因rs17782313多态位点与血清LEP、ADP、IL-6的相关性。结果与对照组比较,观察组BMI、总胆固醇(TC)、LEP、IL-6水平明显升高,而高密度脂蛋白(HDL)、ADP降低;观察组阳性家族史的比例高于对照组(P<0.05)。观察组及对照组CC基因型者血清LEP、IL-6水平明显高于TC、TT基因型者;CC基因型者ADP水平明显低于TC、TT基因型者(P<0.05)。逐步回归分析显示CHD患者IL-6、LEP水平和MC4R基因rs17782313位点基因突变呈现正相关(r=0.801、0.763,P<0.05);观察组ADP水平和MC4R基因rs17782313位点基因多态性呈负相关(r=-0.297,P<0.05)。结论 CHD患者血清瘦素、白介素6水平升高,脂联素水平降低。MC4R基因rs17782313位点突变可能通过影响血清瘦素、脂联素、白介素6水平与CHD的发生发展有关。

Objective To explore the relationship and the significance between rs17782313 site polymorphism of melanocortin-4 receptor（MC4R） gene and serum leptin（LEP）, adiponectin（ADP） and interleukin-6（IL-6）levels in patients with coronary heart disease（CHD）. Methods rs11084753 site polymorphism of MC4 R was detected by DNA sequencing technology in 416 patients with CHD（the study group） and 400 healthy subjects（the control group）, which were divided into TT, TC and CC genotypes according to the mutations of rs17782313 site. The levels of serum LEP, ADP, IL-6 were determined by ELISA. The levels of serum lipids and body mass index（BMI） were measured simultaneously. Stepwise multiple regression analysis was applied to explore the correlation between rs17782313 polymorphism of MC4 R gene and serum LEP, ADP, IL-6 levels. Results The serum levels of BMI, total cholesterol（TC）, LEP, IL-6 in the study group were higher than those in the control group, while the levels of high density lipoprotein（HDL） and ADP were lower（P〈0.05）. The levels of LEP, IL-6 were higher, and the level of ADP was lower in the patients with CC genotype than the patients with TC, TT genotype（P〈0.05）. Stepwise multiple regression analysis showed that rs17782313 site polymorphism of MC4 R was positively correlated with the serum levels of LEP, IL-6 in patients with CHD（r=0.801, 0.763, P〈0.05）, but negatively correlated with ADP（r=-0.297,P〈0.05）. Conclusion Patients with CHD have increased levels of LEP, IL-6 and decreased level of ADP. rs11084753 site polymorphism of MC4 R gene is correlated to CHD through affecting LEP, ADP, IL-6.