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中华妇幼临床医学杂志(电子版) ›› 2016, Vol. 12 ›› Issue (02) : 184 -189. doi: 10.3877/cma.j.issn.1673-5250.2016.02.010

所属专题： 文献；

论著

CYP11A1基因单核苷酸多态性与多囊卵巢综合征的关系
甄鑫1, 颜桂军1, 孙海翔2,*,*(), 王勇3   
  1. 1. 210008　南京大学医学院附属鼓楼医院生殖中心
    3. 210079　南京大学医学院免疫与生殖实验室
  • 收稿日期:2015-10-14 修回日期:2016-02-01 出版日期:2016-04-01
  • 通信作者: 孙海翔

Relationship between polymorphism of CYP11A1 gene and polycystic ovarian syndrome

Xin Zhen1, Guijun Yan1, Haixiang Sun2(), Yong Wang3   

  1. 1. Reproductive Medicine Center, Nanjing Drum Tower Hospital, Affiliated Hospital of Nanjing University Medical School, Nanjing 210008, Jiangsu Province, China
    2. Jiangsu Key Laboratory of Molecular Medicine, Medical School of Nanjing University, Nanjing 210079, Jiangsu Province, China
  • Received:2015-10-14 Revised:2016-02-01 Published:2016-04-01
  • Corresponding author: Haixiang Sun
  • About author:
    Corresponding author: Sun Haixiang, Email:
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甄鑫, 颜桂军, 孙海翔, 王勇. CYP11A1基因单核苷酸多态性与多囊卵巢综合征的关系[J]. 中华妇幼临床医学杂志(电子版), 2016, 12(02): 184-189.

Xin Zhen, Guijun Yan, Haixiang Sun, Yong Wang. Relationship between polymorphism of CYP11A1 gene and polycystic ovarian syndrome[J]. Chinese Journal of Obstetrics & Gynecology and Pediatrics(Electronic Edition), 2016, 12(02): 184-189.

目的

CYP11A1基因单核苷酸多态性(SNP)与多囊卵巢综合征(PCOS)的关系。

方法

选择2005年10月至2010年3月于南京大学医学院附属鼓楼医院妇产科就诊的289例PCOS患者为研究对象，并纳入PCOS组；选择同期于本院参加健康体检的220例健康妇女纳入对照组。采用放射免疫法(RIA)检测患者血清中黄体生成素(LH)、促卵泡生成素(FSH)、雌二醇及睾酮水平等。采用聚合酶链反应-限制性片段长度多态性(PCR-RFLP)法对两组受试者CYP11A1基因SNP rs4077582和rs11632698位点进行基因分型，分析两组受试者的等位基因型频率及等位基因频率，并对年龄、人体质量指数(BMI)及血清性激素水平在不同基因型受试者中进行比较。本研究遵循的程序符合南京大学医学院附属鼓楼医院医学伦理委员会制定的伦理学标准，本研究得到该委员会批准，分组征得受试者本人及其家属的知情同意，并与之签署临床研究知情同意书。

结果

①两组受试者的年龄、BMI等基本资料和FSH、LH、LH/FSH、雌二醇和睾酮等激素水平比较，差异均有统计学意义(P<0.001)。②CYP11A1基因SNP rs4077582等位基因型(CC、CT和TT)在PCOS组患者中的分布分别为24.9%、49.8%和25.3%，而在对照组中分别为34.5%、46.4%和19.1%，二者比较，差异有统计学意义(χ2＝6.399，P＝0.041)。等位基因T在PCOS组中的频率显著高于对照组(χ2＝6.263，P＝0.012)。而CYP11A1基因SNP rs11632698的等位基因型分布在两组受试者中比较，差异无统计学意义(χ2＝3.416，P＝0.181)。③血清学检测结果显示，PCOS组中，CYP11A1基因SNP rs4077582位点3个不同基因型PCOS患者的年龄、BMI等基本资料和各性激素水平比较，差异均无统计学意义(P>0.05)。而在对照组中，LH与LH/FSH在3个不同基因型受试者(CC、CT、TT)间比较，差异有统计学意义(F＝9.362、21.046，P<0.001)。

结论

CYP11A1基因SNP rs4077582位点与PCOS的易感性有关，其作用机制可能是通过调节个体的LH水平最终影响雄激素合成速率，而SNP rs11632698则与PCOS发病无关。

关键词: 胆固醇侧链断裂酶, 多囊卵巢综合征, 多态性，单核苷酸
Objective

To discuss the relationship between CYP11A1 gene single nucleotide polymorphism (SNP) rs4077582 and rs11632698 sites and polycystic ovarian syndrome (PCOS).

Methods

From October 2005 to March 2010, a total of 289 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 220 cases who received physical examination were included as control group.The serum luteinizing hormone (LH), follicle-stimulating hormone (FSH), estradiol and testosterone were detected by radioimmunoassay (RIA). Genotypings of the two SNPs (rs4077582 and rs11632698) were conducted by the polymerase chain reaction-restriction fragment length polymorphism (PCR-RFLP) method. Furthermore, age, body mass index (BMI), and different sex hormone levels among different genotypings were also analyzed. 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 participates.

Results

① There were no significant differences between two groups in the aspects of age, BMI, FSH, LH, LH/FSH, estradiol and testosterone (P<0.001). ②The genotypic distribution (CC, CT and TT)of CYP11A1 gene SNP rs4077582 site were 24.9%, 49.8% and 25.3% in PCOS group, and 34.5%, 46.4% and 19.1% in control group, which with significant difference (χ2=6.399, P=0.041). The frequency of the T allele in PCOS group was significantly higher than that in control group (χ2=6.263, P=0.012). However, no significant difference was found in terms of SNP rs11632698 (χ2=3.416, P=0.181). ③LH and LH/FSH levels were different among the three genotypes (CC, CT, TT) in control group (F=9.362, 21.046; P<0.001).

Conclusions

CYP11A1 gene SNP rs4077582 site is associated with the susceptibility of PCOS. Moreover, the genotype of SNP rs4077582 is associated with serum LH levels, which may alter the testosterone levels and ultimately lead to PCOS.

Key words: Cholesterol side-chain cleavage enzyme, Polycystic ovary syndrome, Polymorphism, single nucleotide
表1 PCOS组和对照组受试者一般情况比较(±s)
组别 例数 年龄(岁) BMI(kg/m2) FSH(IU/L) LH(IU/L) LH/FSH 雌二醇(ng/mL) 睾酮(μg/L)
PCOS组 289 25.8±5.6 23.3±3.7 5.9±3.9 11.8±7.2 2.0±1.2 84.6±45.9 2.1±1.0
对照组 220 32.8±6.2 22.1±3.3 7.5±3.4 5.4±4.9 0.7±0.5 65.0±61.1 1.3±0.6
t值 　 －13.335 3.796 －4.843 11.335 15.099 4.133 10.511
P值 　 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001 <0.001
表2 PCOS组和对照组CYP11A1基因SNP rs4077582位点各等位基因型频率及等位基因频率分布[例数(%)]
组别 例数 等位基因型频率 等位基因频率
CC CT TT C T
PCOS组 289 72(24.9) 144(49.8) 73(25.3) 288(49.8) 290(50.2)
对照组 220 76(34.5) 102(46.4) 42(19.1) 254(57.7) 186(42.3)
χ2值 　 6.399 6.263
P值 　 0.041 0.012
表3 PCOS组和对照组CYP11A1基因SNP rs11632698位点各等位基因型及等位基因频率分布[例数(%)]
组别 例数 等位基因型频率 等位基因频率
AA AG GG A G
PCOS组 289 159(57.2) 112(40.3) 18(6.5) 430(74.4) 148(25.6)
对照组 220 138(62.7) 73(33.2) 9(4.1) 349(79.3) 91(20.7)
χ2值 　 3.416 6.263
P值 　 0.181 0.066
表4 PCOS组CYP11A1基因SNP rs4077582位点各等位基因型患者的基本资料及性激素水平比较(±s)
等位基因型 例数 年龄(岁) BMI(kg/m2) FSH(IU/L) LH(IU/L) LH/FSH 睾酮(μg/L) 雌二醇(ng/L)
CC 72 26.3±6.3 22.9±4.1 5.8±1.8 12.2±8.8 2.1±1.3 1.8±2.2 78.9±27.6
CT 144 25.1±5.8 23.7±3.9 6.1±2.7 11.4±5.9 1.9±1.5 2.3±1.4 88.2±45.4
TT 73 26.5±5.9 23.0±5.2 5.5±2.9 12.2±9.2 2.2±2.0 1.9±1.7 83.3±54.3
F值 　 1.745 1.102 1.368 0.399 0.959 2.573 1.103
P值 　 0.180 0.427 0.253 0.715 0.509 0.129 0.337
表5 对照组CYP11A1基因SNP rs4077582位点各等位基因型患者的基本资料及性激素水平比较(±s)
等位基因型 例数 年龄(岁) BMI(kg/m2) FSH(IU/L) LH(IU/L) LH/FSH 睾酮(μg/L) 雌二醇(ng/L)
CC 76 32.6±5.2 22.1±3.7 7.1±2.6 4.3±2.3 0.6±0.3 1.2±0.6 61.3±50.6
CT 102 32.9±5.3 21.9±4.1 7.4±2.5 6.7±5.2 0.9±0.4 1.3±0.6 69.3±46.3
TT 42 32.5±5.6 22.2±2.8 8.1±3.8 4.4±3.2 0.5±0.5 1.1±0.9 61.4±68.4
F值 　 0.113 0.118 1.707 9.362 21.046 1.434 0.627
P值 　 0.888 0.944 0.182 <0.001 <0.001 0.228 0.532
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