Shen Yang, Xu Qian, Ren Mulan, Cai Yunlang, Xu Jie
Department of Obstetrics and Gynecology, Zhongda Hospital, School of Medicine, Southeast University, Nanjing, China.
J Obstet Gynaecol Res. 2014 Apr;40(4):1077-84. doi: 10.1111/jog.12275. Epub 2013 Dec 10.
To explore the relationship between estrogen metabolism enzyme gene polymorphism and susceptibility to uterine fibroids, and to seek the screening molecular markers for genetic traits in uterine fibroid populations.
A total of 300 female Han Chinese patients and 300 healthy female Han Chinese volunteers in Nanjing (age range, 30-50 years) were recruited from Zhongda Hospital, Southeast University from February 2011 to March 2012. The single nucleotide polymorphisms (SNP) of estrogen-metabolizing enzyme genes from the two groups of women were examined by polymerase chain reaction denaturing high-performance liquid chromatography, which were four COMT gene loci including rs3087869, rs165774, rs165599 and rs4680, three CYP1A1 gene loci including rs1048943, rs4646421 and rs4646422, and three CYP1B1 gene loci including rs1056827, rs1056836 and rs1056837. Genotype frequencies among cases and controls were calculated and analyzed by binary logistic regression.
Regression analysis of SNP showed that COMT IVS1+2329C>T (odds ratio [OR], 2.872; 95% CI, 1.690-4.882) and Val158Met (OR, 2.593; 95% CI, 1.546-4.350), CYP1A1 Ile462Val (OR, 2.383; 95% CI, 1.418-4.005) and Gly45Asp (OR, 2.489; 95% CI, 1.49-4.159), and CYP1B1 Ala119Ser (OR, 3.361; 95% CI, 2.035-5.552) and Leu432Val (OR, 0.164; 95% CI, 0.061-0.441) influenced uterine fibroids significantly (P < 0.05). Allele and genotype frequencies among cases and control were calculated and examined to match the Hardy-Weinberg equilibrium with the χ²-test.
The genetic polymorphisms of IVS1+2329C>T and Val158Met loci in COMT, Ile462Val and Gly45Asp loci in CYP1A1 and Ala119Ser loci in CYP1B1 were risk factors for uterine leiomyoma development, and Leu432Val locus in CYB1B1 may be a protective factor. The results provide a theoretical basis for genetic screening and early intervention for uterine leiomyoma-susceptible populations.
探讨雌激素代谢酶基因多态性与子宫肌瘤易感性之间的关系，寻找子宫肌瘤人群遗传特征的筛查分子标志物。
2011年2月至2012年3月，从东南大学附属中大医院招募了300例汉族女性患者和300名健康汉族女性志愿者（年龄范围30 - 50岁）。采用聚合酶链反应变性高效液相色谱法检测两组女性雌激素代谢酶基因的单核苷酸多态性（SNP），其中包括COMT基因的4个位点，即rs3087869、rs165774、rs165599和rs4680；CYP1A1基因的3个位点，即rs1048943、rs4646421和rs4646422；CYP1B1基因的3个位点，即rs1056827、rs1056836和rs1056837。计算病例组和对照组的基因型频率，并通过二元逻辑回归进行分析。
SNP的回归分析显示，COMT基因的IVS1 + 2329C>T（比值比[OR]，2.872；95%可信区间[CI]，1.690 - 4.882）和Val158Met（OR，2.593；95% CI，1.546 - 4.350）、CYP1A1基因的Ile462Val（OR，2.383；95% CI，1.418 - 4.005）和Gly45Asp（OR，2.489；95% CI，1.49 - 4.159）以及CYP1B1基因的Ala119Ser（OR，3.361；95% CI，2.035 - 5.552）和Leu432Val（OR，0.164；95% CI，0.061 - 0.441）对子宫肌瘤有显著影响（P < 0.05）。计算并检验病例组和对照组的等位基因和基因型频率，以通过χ²检验符合哈迪 - 温伯格平衡。
COMT基因的IVS1 + 2329C>T和Val158Met位点、CYP1A1基因的Ile462Val和Gly45Asp位点以及CYP1B1基因的Ala119Ser位点的基因多态性是子宫肌瘤发生的危险因素，而CYB1B1基因的Leu432Val位点可能是保护因素。研究结果为子宫肌瘤易感人群的遗传筛查和早期干预提供了理论依据。
