雌激素代谢酶基因单核苷酸多态性与子宫肌瘤易感性的病例对照研究

Case-control Study for Estrogen Metabolic Enzyme Gene SNPs and Susceptibility to Uterine Leiomyoma

目的：探讨雌激素代谢酶基因单核苷酸多态性（SNPs）与子宫肌瘤易感性间的关系，以期从分子水平寻找子宫肌瘤特质人群。方法：选择2011年2月至2012年3月于东南大学附属中大医院就诊，居住在南京地区的汉族女性（年龄30～50岁）子宫肌瘤患者及健康女性志愿者各300例为病例组及对照组。采用聚合酶链反应一高效变性液相色谱法（PCR．DHPLC）对两组人群的雌激素代谢酶基因COMT的rs3087869（IVSl＋2329C〉T）、rsl65774（IVS5＋739G〉A）、rsl65599（3’UTR242G〉A）、rs4680（vall58met）4个位点，CYPlA1的rsl048943（11e462Val）、rs4646421（IVSl-726C〉T）、rs4646422（Gly45Asp）3个位点，CYPlB1的rsl056827（Alal19Ser）、rsl056836（Leu32Val）、rsl056837（Asp449Glu）3个位点的多态性进行检测。两组人群的雌激素代谢酶基因分布频率采用卡方检验进行统计分析。结果：分析表明rs3087869（OR：2．872，95％CI：1．690～4．882），rsl65774（OR：2．322，95％CI：1．330～4．056），rs4680（OR：2．59395％CI：1．546～4．350）．rsl048943（OR：2．383，95％CI：1．418～4．005），rs4646422（OR：2．489，95％CI：1．49～4．159），rsl056827（OR：3．361，95％CI：2．035～5．552）与子宫肌瘤发生明显相关（P〈0．05）。统计学分析表明病例组和对照组基因型和等位基因频率符合Hardy-Weinberg平衡。结论：rs3087869、rsl65774、rs4680、rsl048943、rs4646422、rsl056827位点的基因多态性可能是子宫肌瘤的易感因素，与子宫肌瘤发病相关。

Objective：To explore the relationship between estrogen metabolism enzyme gene polymor phism and susceptibility to uterine leiomyoma,to seek the screening markers for uterine leiomyoma genetic trait crowd at the molecular level. Methods：A total of 300 female Han Chinese patients with uterine leiomyo ma（study group）and 300 healthy female Han Chinese volunteers（control group）in Nanjing（ age range,30 ～ 50 years）were recruited from Zhongda Hospital, Southeast University from February 2011 to March 2012. The SNPs of estrogen-metabolizing enzyme genes of the women in the two groups were examined by the polymerase chain reaction-denaturing high-performance liquid chromatography （ PCR-DHPLC）, which were four COMT gene loci including rs3087869, rs165774, rs165599, rs4680, and three CYP1A1 gene loci inclu- ding rs1048943, rs4646421, rs4646422, three CYP1 B1 gene loci including rs1056827, rs1056836, rs1056837. Genotype frequencies among cases and controls were calculated and analyzed with Chi-square test. Resuits.The analysis of SNPs showed that COMT rs3087869 （ OR. 2. 872,95% C1.1. 690 -4. 882 ）, rs165774 （ OR.2. 322,95% C I, 1. 330 ～ 4. 056 ） and rs4680 （ OR：2. 593,95% C I; 1. 546 ～ 4. 350 ）, CYP1 A1 rs1048943 （ OR.2. 383, 95% CI. 1. 418 ～ 4. 005 ） and rs4646422 （ OR; 2. 489,95% CI. 1.49 ～ 4. 159 ）, and CYP1B1 rs1056827（ OR,3. 361,95% CI ;2. 035～5. 552）were significantly related to the onset of uterine fibroids（ P 〈 0.05）. Allele and genotype frequencies among cases and control were calculated and examined to match the Hardy-Weinberg equilibrium with the chi-square test. Conclusions.The genetic polymorphisms of rs3087869, rs165774, rsrs1048943, rs4646422, rs1056827 loci were relative factors for the onset of uterine leiomyoma.