血管紧张素转换酶基因I/D多态性与多囊卵巢综合征的关系

Relationship between I/D polymorphism of angiotensin-converting enzyme gene and polycystic ovarian syndrome

目的探讨血管紧张素转换酶(ACE)基因插入/缺失(I/D)多态性与多囊卵巢综合征(PCOS)的关系。方法选择2007年5月至2011年3月,于南京大学医学院附属鼓楼医院妇产科就诊的217例PCOS患者为研究对象,纳入PCOS组。选择同期于本院参加健康体检的188例妇女,纳入对照组。采集2组受试者的血液标本。采用放射免疫法,检测2组受试者血清促黄体激素(LH)、卵泡刺激素(FSH)、雌二醇、睾酮水平。采用聚合酶链反应-限制性片段长度多态性法,对2组受试者ACE基因I/D多态性基因型进行检测。统计学比较2组受试者的年龄、人体质量指数(BMI)、ACE基因I/D多态性不同基因型及等位基因频率,并分别对ACE基因I/D多态性不同基因型的PCOS组和对照组受试者的年龄、BMI及血清性激素水平进行统计学比较。本研究经过南京大学医学院附属鼓楼医院医学伦理委员会批准,分组征得受试者知情同意,并与之签署临床研究知情同意书。2组受试者月经初潮年龄等基本临床资料比较,差异均无统计学意义(P>0.05)。结果 (1)PCOS组受试者的年龄、血清FSH水平均低于对照组,BMI及血清LH、雌二醇、睾酮水平均高于对照组,并且差异均有统计学意义(t=-12.630、6.528、-3.961、12.091、6.534、19.888,P<0.001)。(2)PCOS组受试者I/D多态性DD、ID和Ⅱ基因型频率分别为28.1%、48.8%和23.0%,对照组分别为21.8%、54.2%和23.9%,2组I/D多态性DD、ID和Ⅱ基因型频率比较,差异无统计学意义(χ~2=2.196,P=0.333)。PCOS组受试者D等位基因频率为52.5%,对照组为48.9%,2组比较,差异无统计学意义(χ~2=1.044,P=0.307)。(3)PCOS组中,ACE基因I/D多态性不同基因型(DD、ID和ID基因型)受试者的年龄、BMI及血清FSH、雌二醇水平比较,差异均无统计学意义(P>0.05);ACE基因I/D多态性不同基因型受试者的血清LH、睾酮水平及LH与FSH比值(LH/FSH)比较,差异均有统计学意义(F=14.721、19.609、20.685,P<0.001);而两两比较结果显示,DD与ID基因型受试者的血清LH、睾酮水平及LH/FSH,均显著高于Ⅱ基因型受试者,差异亦均有统计学意义(DD基因型与Ⅱ基因型比较:LSD-t=4.416、5.545、4.324,P<0.001;ID基因型与Ⅱ基因型比较:LSD-t=5.195、5.692、6.413,P<0.001)。在对照组中,ACE基因I/D多态性不同基因型受试者的年龄、BMI及血清FSH、LH、睾酮、雌激素水平及LH/FSH比较,差异均无统计学意义(P>0.05)。结论 ACE基因I/D多态性与PCOS的易感性无关,但等位基因D可能与高血清睾酮、LH水平有关。由于本研究纳入样本量相对较小,ACE基因I/D多态性与PCOS的关系,仍需大样本、多中心、随机对照研究进一步试验、证实。

Objective To explore the relationship between I/D polymorphism of angiotensin-converting enzyme （ACE） gene and polycystic ovarian syndrome （PCOS） .Methods From May 2007 to March 2011 ,a total of 217 cases with PCOS who were admitted to Nanjing Drum Tower Hospital , Affiliated Hospital of Nanjing University Medical School were included into this study as PCOS group .Meanwhile ,another 188 cases who received physical examinations were included as control group .The blood samples of two groups were collected . The serum luteinizing hormone （LH ） , follicle-stimulating hormone （ FSH ） , estradiol and testosterone levels were measured by radioimmunoassay method . Genotypings of the ACE gene polymorphism were conducted by the polymerase chain reaction-restriction fragment length polymorphism method .The age ,body mass index （BMI） ,frequencies of genotype and allele of ACE gene I/D polymorphism between two groups , and age ,BMI ,levels of serum gonadal hormones among different I/D genotypings in PCOS group and control group were statistically compared .The study protocol was approved by the Ethical Review Board of Investigation in Human Being of Nanjing Drum Tower Hospital , Affiliated Hospital of Nanjing University Medical School .Informed consent was obtained from each participants .There were no significant differences between two groups in the basic clinical data ,such as menarche age and so on （P〉0 .05） .Results ①The age and level of serum FSH in PCOS group were lower than those in control group ,while the BMI ,levels of serum LH ,estradiol and testosterone in PCOS group were all higher than those in control group ,and all the differences were statistically significant （t=-12 .630 ,6 .528 ,-3 .961 ,12 .091 ,6 .534 ,19 .888;P〈0 .001） .②The frequencies of DD ,ID ,and II genotype of ACE gene in PCOS group were 28 .1% ,48 .8% ,23 .0% ,respectively ,and 21 .8% , 54.2% ,23 .9% ,respectively in control group ,there was no significant difference between two groups in the genotype frequency （χ2 =2 .196 , P= 0 .333） .The frequency of D allele in PCOS group was 52.5% ,and 48 .9% in control group ,there was no significant difference between two groups in the allele frequency either （χ2 = 1.044 , P= 0 .307 ） . ③ In PCOS group , there were no significant differences in the age ,BMI ,levels of serum FSH and estradiol among different I/D genotypes （DD , ID and II genotypes） （P〉 0 .05）;while as to the levels of serum LH ,testosterone and LH/FSH ratio ,all the differences were statistically significant （F= 14 .721 ,19.609 ,20 .685 ;P〈 0 .001） , multiple comparison results showed that levels of serum LH ,testosterone and LH/FSH ratio of PCOS patients with DD and ID genotype ,were significantly higher than those of PCOS patients with II genotype ,and the differences were also statistically significant （DD genotype vs II genotype：LSD-t=4.416 ,5.545 ,4.324 ,P〈 0.001 ;ID genotype vs II genotype：LSD-t= 5.195、5.692、6.413 ;P〈0.001） . There were no significant differences in the age , BMI , levels of serum FSH , LH , testosterone ,estrogen and LH/FSH ratio among subjects with different I/D genotypes in control group （P〉0 .05） .Conclusions ACE gene I/D polymorphism is not associated with the susceptibility of PCOS ,but the allele D may contribute to the high levels of serum testosterone and LH .As the sample size in this study is relatively small ,the association of A CE gene I/D polymorphism and PCOS still requires large sample ,multicenter ,and randomized controlled studies to confirm .