多囊卵巢综合征患者对氧磷酶1基因-108 C/T多态性的研究

The-108 C/T Polymorphism in Paraoxonase 1 Gene in Chinese Patients with Polycystic Ovary Syndrome

目的研究对氧磷酶1基因(PON1)调控区-108位点C/T多态性是否与中国妇女多囊卵巢综合征(PCOS)有关联,为阐明PCOS的分子遗传基础提供依据。方法应用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)技术对中国成都地区346例PCOS患者和315例对照妇女PON1基因-108位点C/T多态性进行了分析。用化学发光法测定血清总睾酮(TT)、黄体生成素(LH)、促卵泡激素(FSH)和血浆胰岛素(INS);用酶法试剂盒测定血糖(GLU)、总胆固醇(TC)、甘油三酯(TG)、高密度脂蛋白胆固醇(HDL-C)、低密度脂蛋白胆固醇(LDL-C);用微量丙二醛测定试剂盒测定血清丙二醛(MDA)浓度。结果 PCOS组PON1基因-108位点CC、CT、TT基因型频率分别为:0.283、0.517、0.199,C和T等位基因频率分别为:0.542和0.458;对照组该位点CC、CT、TT基因型频率分别为:0.324、0.492、0.184,C和T等位基因频率分别为:0.570和0.430,两组间基因型和等位基因频率差异无统计学意义(P>0.05)。在对照组,CT基因型亚组F-G评分和餐后2h血糖(GLU120)水平高于CC基因型亚组(P<0.05),TT基因型亚组FSH水平和血清MDA浓度高于CC基因型亚组(P<0.05),在调整了年龄和BMI以后,FSH、GLU120和MDA的差异仍然有统计学意义(P=0.006、0.033和0.047)。在PCOS患者组,CT基因型亚组动脉硬化指数(AI)高于CC基因型亚组(P=0.038),但在调整年龄和BMI以后,差异不再有统计学意义(P=0.053)。结论 PON1基因调控区-108位点C/T多态性与对照妇女糖代谢、生殖激素水平及氧化应激有一定关联性,但未发现该位点与中国成都地区PCOS的发病有关。

Objective To investigate the relationship between the-108 C/T polymorphism in the promoter of paraoxonase 1（PON1） gene and polycystic ovarian syndrome（PCOS） in Chinese women.Methods A total of six hundred and sixty one subjects（346 patients with PCOS and 315 healthy control women） in Chengdu area were included in this study.The-108 C/T polymorphism in PON1 gene wasstudied using polymerase chain reaction and restriction fragment length polymorphism analysis（PCR-RFLP）.Total testosterone（TT）,luteinizing hormone（LH）,follicle stimulating hormone（FSH） and plasma insulin（INS） were determined by chemiluminescent method.Plasma glucose（GLU）,total cholesterol（TC）,triglycerides（TG）,high density lipoprotein cholesterol（HDL-C）,and low density lipoprotein cholesterol（LDL-C） were measured by enzymatic assay.Serum malondialdehyde（MDA） levels were measured by spectrophometry at 532 nm using micro-MDA detection kits.Results The frequencies of CC,CT and TT genotypes at PON1-108 C/T site in PCOS and control groups were 0.283 and 0.324,0.517 and 0.492,0.199 and 0.184,respectively,and the frequencies of C and T alleles in both groups were 0.542 and 0.570,0.458 and 0.430,respectively.There were no significant differences in the frequencies of the genotypes and alleles between PCOS and control groups（P〉0.05）.In the control group,the subjects with genotype CT had higher F-G scores and plasma glucose levels at 2 h during OGTT（75 g glucose） when compared with those of genotype CC（P〈0.05）.Higher FSH level and MDA concentration also observed in those of genotype TT by compared with those of CC genotype（P〈0.05）.The differences in FSH,GLU120 and MDA levels remained significant after adjustment for age and BMI（P=0.006,0.033 and 0.047,respectively）.In the PCOS group,the patients with genotype CT had higher atherogenic index（AI） when compared with those of genotype CC（P=0.038）,but this difference was not significant after adjustment for age and BMI（P=0.053）.Conclusion This study indicated that the-108 C/T polymorphism in the promoter of PON1 gene was associated with hormonal levels,glucose metabolism and oxidative stress in the control women,but not associated with PCOS in Chinese women of Chengdu area.