白细胞介素1与多囊卵巢综合征肥胖的相关性

目的 探讨炎症细胞因子——白细胞介素1(IL-1)β亚型(IL-1β)和IL-1受体拮抗剂(IL-1ra)与多囊卵巢综合征(PCOS)患者肥胖发生的关系.方法(1)2006年10月至2007年1月,选择在北京大学第三医院生殖医学中心就诊的PCOS患者118例,根据WHO国际肥胖特别工作组2000年提出的亚太地区肥胖标准体质指数(BMI)≥25 kg/m2]分为PCOS肥胖组56例,PCOS非肥胖组62例.采用PCR技术检测IL-1β基因-511位点、第5外显子位点和IL-1 ra基因第2内含子的基因多态性.(2)随机抽取PCOS肥胖组患者29例和PCOS非肥胖组患者31例,采用ELISA法检测血清IL-1β、IL-1ra水平,并测定空腹血糖(FBG)、空腹胰岛素(FINS)、超敏C反应蛋白水平和白细胞计数.结果(1)基因型和等位基因频率:PCOS肥胖组患者IL-1β基因-511位点T/T基因型频率及T等位基因频率分别44.6％和63.4％,PCOS非肥胖组患者分别为11.3％和39.5％,两组分别比较,差异均有统计学意义(P＜0.05);PCOS肥胖组患者IL-1 ra基因Ⅰ/Ⅴ基因型频率及Ⅴ等位基因频率分别为19.6％和9.8％,PCOS非肥胖组分别为3.2％和1.6％,两组分别比较,差异也均有统计学意义(P＜0.05).(2)血清学检测结果:PCOS肥胖组患者血清IL-1β水平为(149±36)ng/L,高于PCOS非肥胖组患者的(96±42)ng/L,PCOS肥胖组患者IL-1 ra水平为(284±97)ng/L,高于PCOS非肥胖组患者的(208±84)ng/L,两组分别比较,差异均有统计学意义(P＜0.05).PCOS肥胖组患者FBG、FINS、超敏C反应蛋白水平和白细胞计数分别为(5.1±0.7)mmol/L、(17±9)mU/L、(1.5±0.6)mg/L、(7.0±2.3)×109/L,PCOS非肥胖组患者分别为(4.9±0.5)mmol/L、(11 ±8)mU/L、(0.9 ±0.4)mg/L、(5.9±1.3)×109/L,两组间各项指标分别比较,差异均有统计学意义(P＜0.05).(3)IL与BMI的相关性:PCOS患者血清IL-1β(r=0.673)、IL-1ra(r =0.557)与BMI呈线性正相关(P均＜0.05).结论 炎症因子IL-1β和IL-1ra与PCOS患者肥胖的发生明显相关,IL-1β基因-511位点携带T等位基因和IL-1ra基因携带等位基因Ⅴ的PCOS患者更有发生肥胖的倾向.

Correlation between interleukin-1 and the obesity of polycystic ovary syndrome

Objective To investigate the correlation between interleukin-1β(IL-1β),interleukin-1 receptor antagonist(IL-1 ra)and the obesity of polycystic ovary syndrome(PCOS).Methods(1)From Oct.2006 to Jan.2007,118 PCOS patients were enrolled in this study in Peking University Third Hospital,which were divided into 56 patients in obese PCOS group and 62 patients in non-obese PCOS group according to the WHO International Obesity Task Force Asia-Pacific criteriabody mass index(BMI)25 kg/m2].The polymorphism of IL-1β gene promoter region,exon-5 and intron 2 of IL-1 ra gene were detected by PCR.(2)Twenty-nine obese PCOS patients and 31 non-obese PCOS patients were selected randomizedly serum levels of IL-1β,IL-1 ra were measured by ELISA,in the mean time,serum levels of fasting glucose,fasting insulin and the total white blood cell,hypersensitive C-reactive protein levels were measured.Results(1)Genetic test:the frequency of TT genotype and T allele of IL-1β promoter region(-511)in obese PCOS patients were significantly higher than those in non-obese patients(44.6％ vs.11.3％,63.4％ vs.39.5％,all P ＜0.05).The frequency of IL-1 ra Ⅰ / Ⅴ genotype and Ⅴ allele of IL-1 ra gene were 19.6％ and 9.8％ in obese PCOS patients,which were significantly higher than those in non-obese group(3.2％ and 1.6％,P ＜0.05).(2)Serological test:serum level of IL-1β and IL-1ra of(149 ±36)and(284 ±97)ng/L in obese PCOS group which were significantly higher than those in non-obese PCOS group(96 ± 42)and(208 ± 84)ng/L,P ＜ 0.05].Fasting blood glucose,fasting insulin and hypersensitive C-reactive protein and white blood cell count were(5.1 ± 0.7)mmol/L,(17 ± 9)mU/L,(1.5 ± 0.6)mg/L and(7.0 ± 2.3)× 109/L in obese PCOS group,which were significantly higher than in non-obese PCOS group(4.9 ±0.5)mmol/L,(11 ±8)mU/L,(0.9 ±0.4)mg/L and(5.9 ±1.3)× 109/L,P＜0.05].(3)The correlation between interleukin and BMI: serum levels of IL-1β(r =0.673)and IL-1 ra(r =0.557)were positively correlated with BMI in PCOS patients(P ＜ 0.05).Conclusions Inflammatory factors IL-1β and IL-1ra had correlation with obesity of PCOS patients,PCOS patients who carried T allele of IL-1β gene promoter region(-511)and Ⅴ allele of IL-1ra gene were high risk of obesity.